Events

Prof. Igor Ulitsky, Department of Immunology and Regenerative Biology, Faculty of Biology, WIS

Dr. Shay Covo, Department of Plant Pathology and Microbiology Faculty of Agriculture, Food & Environment The Hebrew University of Jerusalem

Prof. Andreas Marx, Department of Chemistry and Konstanz Research School Chemical Biology, University of Konstanz Germany

Prof. Mattan Hurevich, Institute of Chemistry Hebrew University

Dr. Jerome Tubiana, Blavatnik School of Computer Science, Tel Aviv University

Prof. Emmanuel Levy, Dept. of Chemical and Structural Biology Weizmann Institute

Prof. Dina Schneidman, School of Computer Science and Engineering The Hebrew University

Dr. Saurav Mallik, Prof. Emmanuel Levy's lab Dept. of Chemical & Structural Biology WIS

Dr. Rina Rosenzweig, Department of Chemical & Structural Biology, Faculty of Chemistry, WIS

Dr. Moran Shalev-Benami, Department of Chemical & Structural Biology, Faculty of Chemistry, WIS

Rhodopsins are a ubiquitous family of light sensing/signaling proteins. In recent work, our group discovered an intriguing family of rhodopsins in algae: the bestrhodopsins. Through cryo-EM and comprehensive biochemical and electrophysiological studies, we showed that bestrhodopsins are fusions of rhodopsins and ion channels which assemble as mega-complexes to enable light-controlled passage of ions across membranes. Regulation of a classical ion channel by an attached photoreceptor has never been found before in nature, and previous attempts to engineer light-regulated fused channels have yielded limited success. The discovery and characterization of bestrhodopsins thus provide a new template for designing proteins with light-sensing and ion-conducting activities, as well as represent a platform for regulating cellular signaling in living organisms using light. These findings are therefore not only important as a basic scientific discovery but also for the field of optogenetics where neural activity is controlled by light. In the present talk, I will present the discovery of the bestrhodopsins, and explain how we use our cryo-EM work for structure-based design of dramatically improved tools to manipulate signaling cascades in cells by light control, paving the way for the next generation of optogenetics tools to study brain function in vivo.

Dr. Tanaya Bose, Yonath Lab, Dept. of Chemical and Structural Biology, Weizmann Institute

Dr. Shifra Lansky, Cornell University, New York

Transient receptor potential (TRP) channels are a large, eukaryotic ion-channel superfamily that control diverse physiological functions. To date, more than 210 structures from over 20 TRP-channels have been determined, all are tetramers. Using high-speed atomic force microscopy (HS-AFM), a pioneering technique capable of “filming” single-molecule proteins, we discovered a rare and transient pentameric state for TRPV3, and determined the pentamer structure using single-particle cryo-EM. Our results suggest that the pentamer relates to the pore-dilated state, a structurally-elusive state characterized by increased conductance and permeability to small molecules. These findings lay the foundation for many new directions in ion-channel research, and demonstrate the strength of HS-AFM in discovering transient and rare states of proteins.

Dr. Frida Belinky, Virus Persistence and Dynamics Section Immunology Laboratory Vaccine Research Center National Institute of Allergy and Infectious Diseases National Institutes of Health

Prof. Eyal Arbely, Department of Chemistry Ben Gurion University

Dr. Ingo Hartung, Head of Medicinal Chemistry & Drug Design Global Research & Development Merck Healthcare KGaA

Prof. Xiaoguang Lei, Peking University

Prof. Karl Gademann, Department of Chemistry University of Zurich

Prof. Daniel Minor, Departments of Biochemistry & Biophysics University of California San Francisco

Dr. Milana Frenkel-Morgenstern, Azrieli Faculty of Medicine Bar-Ilan University

Prof. John Moult, Institute of Bioscience and Biotechnology Research Department of Cell Biology and Molecular Genetics University of Maryland

Guy Zoltsman, Dept. of Chemical & Structural Biology Weizmann Institute

Prof. Wladek Minor, Department of Molecular Physiology and Biological Physics University of Virginia

Prof. Yitzhak Tor, University of California San Diego

Nava Reznik, Fass Lab Dept. of Chemical & Structural Biology Weizmann Institute

Prof. Rouslan Efremov, VIB-VUB Center for Structural Biology Belgium

Prof. Barry Honig, Columbia University

Prof. Eyal Nir, Department of Chemistry Ben-Gurion University

Dr. Moran Frenkel-Pinter , Institute of Chemistry The Hebrew University of Jerusalem

Dr. Eitan Lerner, The Alexander Silberman Institute of Life Sciences The Hebrew University

Dr. Aubry Miller, Cancer Drug Development German Cancer Research Center DKFZ, Germany

Prof. Oliver P. Ernst, University of Toronto Canada

Prof. Shuguang Zhang, MIT Media Lab USA

Dr. Joshua M. Grolman, Materials Science and Engineering Technion - Israel Institute of Technology

Dr. Nir Hananya, Department of Chemistry Princeton University

Prof. Uri Raviv, Institute of Chemistry The Hebrew University of Jerusalem

Prof. Yossi Weizmann, Department of Chemistry Ben-Gurion University

Prof. G. Marius Clore, NIH Bethesda, Maryland USA

Prof. John A. Tainer, Department of Molecular and Cellular Oncology Division of Basic Science Research The University of Texas MD Anderson Cancer Center Houston, TX

Dr. Shahar Sukenik, Dept. of Chemistry and Chemical Biology University of California

Prof. Dmitry Ivankov, Center for Molecular and Cellular Biology Skoltech University Russia

Prof. Joerg Enderlein, Georg-August-University Goettingen, Germany

Prof. Remo Rohs, The Department of Quantitative and Computational Biology University of Southern California

Prof. Loren D. Williams, Center for the Origins of Life School of Chemistry and Biochemistry Georgia Tech, Atlanta

Prof. Michel Bouvier, Institute for Research in Immunology and Cancer (IRIC) of the Université de Montréal (UdeM)

Prof. Doron Gerber, Faculty of Life Science Bar-Ilan University

KENDREW LECTURE: Prof. Pamela Bjorkman, California Institute of Technology

Prof. Stefan Rudiger, Bijvoet Center for Biomolecular Research Utrecht University

Prof. Amir Aharoni, Dept. of Life Sciences Ben-Gurion University

Prof. Israel Sekler, The Dept. of Physiology and Cell Biology Faculty of Health Sciences Ben-Gurion University of the Negev

Prof. Yuval Ebenstein, School of Chemistry Tel-Aviv University

Prof. Sander Tans, Dept. of Bionanoscience Delft University of Technology The Netherlands

Prof. Anne Wentink, Institute of Chemistry Leiden University Netherlands

Dr. Ariel Afek, Dept. of Chemical and Structural Biology Weizmann Institute

Prof. Ariel Kaplan, Faculty of Biology Technion

Dr. Lalit Deshmukh, Dept. of Chemistry and Biochemistry University of California San Diego, USA

Prof. Hashim Al-Hashimi, Department of Biochemistry Duke University School of Medicine Durham, NC, USA

Dr. Alice L.B. Pyne, Dept. of Materials Science and Engineering University of Sheffield, UK

Prof. David Sprinzak, School of Neurobiology, Biochemistry and Biophysics, Faculty of Life Sciences, TAU

Prof. Eilon Sherman, Racah Institute of Physics The Hebrew University

Prof. Masha Niv, The Institute of Biochemistry, Food Science and Nutrition Faculty of Agriculture, Food and Environment The Hebrew University

Dr. Assaf Alon, Harvard Medical School

Prof. Michael Glickman, Faculty of Biology, Technion

Dr. Barak Raveh, School of Computer Science and Engineering The Hebrew University of Jerusalem

Prof. Elizabeth Meiering, Department of Chemistry University of Waterloo, Canada

Dr. Nir Fluman, Dept. of Biomolecular Sciences Weizmann Institute of Science

Prof. Ron Naaman, Department of Chemical and Biological Physics Weizmann Institute

Prof. David Eliezer , Weill Cornell Medicine Graduate School of Medical Sciences, NY, USA

Dr. Ariel Afek, Duke Center for Genomic and Computational Biology Duke University NC, USA

Dr. Iris Grossman-Haham, Dept. of Cellular and Molecular Pharmacology University of California, San Francisco

Dr. Paul Emsley, Laboratory of Molecular Biology Cambridge, England

Dr. Liron David, Harvard Medical School

Dr. François-Xavier Theillet, CNRS, Paris-Saclay France

Dr. Michal Shoshan, Group leader in Bioinorganic Chemistry Department of Chemistry, University of Zurich

Dr. Netanel Tzarum, HUJI

Dr. Amit Meir, Yale University

Keren Kahil, Labs of Prof. Lia Addadi & Prof. Steve Weiner Dept. of Structural Biology, WIS

Gabriel Javitt, Prof. Deborah Fass lab Dept. of Structural Biology Weizmann Institute

Dr. Ronen Gabizon, Dr. Nir London lab Dept. of Organic Chemistry Weizmann Institute

Dr. Moran Frenkel-Pinter, NASA Postdoctoral Fellow | Hud, Grover and Williams Labs NSF/NASA Center for Chemical Evolution Georgia Institute of Technology | School of Chemistry and Biochemistry 901 Atlantic Drive | Atlanta, GA 30332

Dr. Galia Ma'ayan, Technion, Haifa

Prof. Daniella Goldfarb, Department of Chemical and Biological Physics, WIS

Prof. Joanna Masel, Ecology and Evolutionary Biology, The University of Arizona, USA

Prof. Jack Taunton, Dept. of Cellular and Molecular Pharmacology, University of California, San-Francisco

Dr. Rotem Rubinstein, Tel-Aviv University

Prof. Mickey Kosslof, Haifa University

Prof. Barry Honig, Columbia University

Prof. Amir Goldbourt, Tel Aviv University

Dr. Xavier Salvatella,

Dr. Nir Kalisman, Dept. of Biological Chemistry The Hebrew University

Dr. Ori Avinoam, Department of Biomolecular Sciences WIS

Prof. Eddy Arnold, Board of Governors Professor and Distinguished Professor of Chemistry and Chemical Biology, Rutgers University

Dr. Ron Orbach, Dept. of Molecular Biophysics & Biochemistry Yale University

Prof. Sophie Jackson, Department of Chemistry University of Cambridge United Kingdom

Prof. V. Samuel Raj, SRM University, Delhi-NCR, Sonepat, India

Prof. Peter Dedecker, KU LEUVEN, BELGIUM

Prof. Elizabeth Meiering, University of Waterloo Canada

Prof. Barak Akabayov, Ben Gurion University

Prof. David Stuart, MRC Professor of Structural Biology, Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford,

Prof. Stephen Blacklow, Harvard Medical School

Dr. Michael Latham, Texas Tech University

Dr. Yoni Haitin, Tel-Aviv University

Prof. Kenji Inaba, Professor of Biochemistry & Structural Biology Institute of Multidisciplinary Research for Advanced Materials, Tohoku University Sendai, Japan

Dr. Tobias Warnecke, Molecular Systems Group MRC London Institute of Medical Sciences (LMS) & Imperial College London

Dr. Stas Engel, Ben Gurion University

Prof. Tommer Ravid, HUJI

Prof. Michael Glickman, Technion

Prof. Neil Bulleid, Director of the Institute of Molecular Cell & Systems Biology University of Glasgow

Prof. Olga Gursky, Boston University School of Medicine

Prof. Eitan Lerner, HUJI

Dr. Dror Chorev, Oxford University, UK

Dr. Ruth Cohen Khait, Oxford University, UK

Prof. Brenda Schulman,

Dr. Monika Bajorek, from INRA, France

Prof. Gary J. Pielak, Department of Chemistry, University of North Carolina at Chapel Hill, USA

Prof. Manuel Prieto , Instituto Superior Técnico, University of Lisbon, Lisbon, Portugal

Prof. Noam Adir, Dean, Schulich Faculty of Chemistry, Technion

Prof. Nahum Sonenberg , Department of Biochemistry McGill University, Montreal CANADA

Dr. Daron Freedberg, Center for Biologic Evaluation and Research, U.S. Food and Drug Administration

Dr. Hugo Schweke,

Prof. Xi Chen,

Prof. Leah Gheber,

Dr. Neta Varsano,

Dr. Norman Metanis,

Prof. Peter Peters, Maastricht Multimodal Molecular Imaging institute (M4I).

Prof. Dave Thirumalai, Department of Chemistry, UT Austin

Dr. Dina Schneidman, Hebrew University

Proteins generally populate multiple structural states in solution. Transitions between these states are important for function, such as allosteric signaling and enzyme catalysis. Structures solved by X-ray crystallography provide valuable, but static, atomic resolution structural information. In contrast, cross-linking mass spectrometry (XLMS) and small angle X-ray scattering (SAXS) datasets contain information about conformational and compositional states of the system. The challenge lies in the data interpretation since the cross-links in the data often comes from multiple structural states. We have developed a novel computational method that simultaneously uncovers the set of structural states that are consistent with a given dataset (XLMS or SAXS). The input is a single atomic structure, a list of flexible residues, and an experimental dataset. The method finds multi-state models (models that specify two or more co-existing structural states) that are consistent with the data. The method was applied on multiple SAXS and XLMS datasets, including large multi-domain proteins and proteins with long disordered fragments. The applicability of the method extends to other datasets, such as 2D class averages from Electron Microscopy, and residual dipolar couplings.

Prof. Jordan Chill, Dept. of Chemistry, BIU

WASP-Interacting Protein (WIP) is a multifunctional key participant in mediating actin-related cytoskeletal changes in human T cells. WIP is also an intrinsically disordered protein (IDP), lacking any significant secondary or tertiary structure across its 503 residues, and thus defies the ordinarily reliable structure-function paradigm. Our research focuses on how interactions between this ‘hub’ multi-tasker and its various structured binding partners delicately control T cell destiny, in particular the role played by disorder-to-order transitions. Three such critical protein-protein contacts involve the WIP N-terminal domain (with actin), a proline-rich central segment (with cortactin) and the C-terminal domain (with Wiskott-Aldrich syndrome protein, WASP). The first two are of intermediate binding energy (KD ~ 50-3000 nM) and transiently modulate WIP interactions with the actin polymerization machinery. In contrast, the latter forms a tight complex with WASP and inhibits both its activity and eventual degradation in a phosphorylation-dependent manner, explaining why the hereditary Wiskott-Aldrich syndrome immunodeficiency results from WASP mutants unable to bind WIP. As an IDP, WIP ‘structure’ is essentially an ensemble of multiple conformations contributing to function, and this complexity gives solution NMR – armed with new IDP-optimized methodologies – unrivaled insight into how IDPs exert their biological influence. We established that transient structure in free WIPN and WIPC echoes their bound conformations, uncovering novel binding epitopes in the process. We also observed subtle ensemble shifts induced by environmental factors, such as temperature, denaturant or crowding agents, revealing the biophysics governing WIP behavior in the cellular environment. We further investigated the largest conformational change, experienced by WIPC upon binding to WASP, by determining the contribution of various WIP epitopes to complex affinity, and eventually the structure of the WIP-WASP complex. Finally, we offer an unexpected structural explanation for phosphorylation-induced dissociation of this complex that may explain how this phospho-switch controls WASP degradation. Taken together our results provide a comprehensive map of WIP structure and dynamics and how these affect its interaction with T cell binding partners, and highlight the great impact of high-resolution NMR studies upon the field of biologically active unstructured proteins.

Prof. Elena Orlova, Institute of Structural and Molecular Biology, Birkbeck College, London

During the last decade electron microscopy become a powerful tool in structural studies of large biological complexes. Cryo electron microscopy enabled us to reveal molecular dynamics of the complexes by analysis of samples in solution. This was made possible by long-standing efforts in sample preparations (cryo-EM imaging), in development of hardware, automation in data collection, methods in image analysis and, eventually, interpretation of results. Here I would like to share my experience in using these approaches in analysis of structural organisation of bacteriophages exemplified by the SPP1 phage. It is important to highlight critical steps in obtaining near-atomic resolution structures of the biocomplexes. We have obtained high resolution structures of main components of the phage such as a capsid and its nano-motor engaged into packaging of genome and its release.

Dr. Dan Some, Wyatt Technology

Prof. Dan T Major, BIU

Dr. Mira Amiram, BGU

Dr. Shlomi Reuveni , TAU

Many fine-scale features of ribosomes have been explained in terms of function, revealing a molecular machine that is optimized for error-correction, speed and control. In this talk, I will demonstrate mathematically that much less understood, larger-scale features of ribosomes—such as why RNA dominates the ribosome mass and why the ribosomal protein content is divided into 55–80 small and similarly sized segments—could all be explained by optimization for self-replication.

Special Seminar

Prof. Ana-Nicoleta Bondar , Molecular Biophysics with research Free University of Berlin

Zohar Eyal , Ph.D. student of Prof. Ada Yonath WIS

Dr. Assaf Gal , Department of plant and environmental sciences WIS

Prof. Arnon Henn,

Dr.Yishai Levin, G-Incpm center WIS

2018 Sir John C. Kendrew Memorial Lecture

Prof. James Berger, Biophysics and Biophysical Chemistry Johns Hopkins University School OF Medicine

Prof. Wayne Hendrickson, Columbia University

Dr. Sarel Fleishman, Department of Biomolecular Sciences WIS

Prof. Carlos Simmerling, Department of Chemistry, Stony Brook University

In contrast to proteins recognizing small-molecule ligands, DNA-dependent enzymes cannot rely solely on interactions in the substrate-binding centre to achieve their exquisite specificity. It is widely believed that substrate recognition by such enzymes involves a series of conformational changes in the enzyme-DNA complex with sequential gates favoring cognate DNA and rejecting nonsubstrates. However, direct evidence for such mechanism is limited to a few systems. We used molecular dynamics simulations to explore the dynamic recognition of oxidative DNA damage by glycosylase enzymes. The resulting energy profiles, supported by biochemical analysis of site-directed mutants disturbing the interactions along the proposed path, show that the glycosylases selectively facilitate recognition by stabilizing several intermediate states, helping the rapidly sliding enzyme avoid full extrusion of every encountered base for interrogation. Lesion recognition through multiple gating intermediates may be a common theme in DNA repair enzymes; we show that human and bacterial enzymes share a common recognition mechansim despite lack of sequence or structural similarity of their glycosylases.

Special Seminar

Prof. Paul Emsley, MRC Laboratory of Molecular Biology UK

Dr. Reuven Wiener, Faculty of Medicine, HUJI

Special seminar

Prof. Garib Murshudov , MRC Cambridge U.K.

Dr. Nir Ben-Tal, TAU

Dr. Bastian Braeuning, Technische Universität München Munich, Bayern, Germany Join institution

Dr. Bastian Braeuning, Technical University of Munich Department of Chemistry

Prof. Shuguang Zhang, Center for Biomedical Engineering, MIT

Structure and function studies of membrane proteins, particularly G protein-coupled receptors (GPCRs) and multiple segment transmembrane proteins, require detergents. Without detergents these integral membrane proteins aggregate and are nearly impossible to analyze. We have devised a useful tool, the QTY Code, for engineering hydrophobic domains to become detergent-free, namely water-soluble, without significantly altering protein structure and function. Here we report using the QTY Code (glutamine, threonine and tyrosine) to systematically replace the hydrophobic amino acids leucine, valine, isoleucine and phenylalanine in the four chemokine receptors CCR5, CXCR4, CCR10 and CXCR7. Our simple QTY Code is a useful tool and has implications for engineering water-soluble variants of previously water-insoluble and perhaps aggregated proteins including amyloids.

Dr. Shahar Sukenik, University of Illinois

Prof. Gonen Ashkenasy, BGU

Prof. Ariel Kaplan, Technion

Prof. Oded Lewinson, Technion

Prof. Benjamin Schuler, University of Zurich

Molecular communication in biology is mediated by protein interactions. According to the current paradigm, the specificity and affinity required for these interactions are encoded in the precise complementarity of binding interfaces. Even proteins that are disordered under physiological conditions or that contain large unstructured regions commonly interact with well-structured binding sites on other biomolecules. We recently discovered the existence of an unexpected interaction mechanism: The two intrinsically disordered human proteins histone H1 and its nuclear chaperone prothymosin α associate in a one-to-one complex with picomolar affinity, but they fully retain their structural disorder, long-range flexibility, and highly dynamic character. Based on the close integration of single-molecule experiments, NMR, and molecular simulations, we obtain a detailed picture of this complex and show that the interaction can be explained by the large opposite net charge of the two proteins without requiring defined binding sites or interactions between specific individual residues

Special Seminar

Prof. Jörg Enderlein, III. Institute of Physics – Biophysics Department of Physics Georg August University Germany

Classical fluorescence microscopy is limited in resolution by the wavelength of light (diffraction limit) restricting lateral resolution to ca. 200 nm, and axial resolution to ca. 500 nm (at typical excitation and emission wavelengths around 500 nm). However, recent years have seen a tremendous development in high- and super-resolution techniques of fluorescence microscopy, pushing spatial resolution to its diffraction-dictated limits and much beyond. One of these techniques is Image Scanning Microscopy (ISM). In ISM, the focus of a conventional laser-scanning confocal microscope (LCSM) is scanned over the sample, but instead of recording only the total fluorescence intensity for each scan position, as done in conventional operation of an LCSM, one records a small image of the illuminated region. The result is a four-dimensional stack of data: two dimensions refer to the lateral scan position, and two dimensions to the pixel position on the chip of the image-recording camera. This set of data can then be used to obtain a super-resolved image with doubled resolution, completely analogously to what is achieved with Structured Illumination Microscopy. However, ISM is conceptually and technically much simpler, suffers less from sample imperfections like refractive index variations, and can easily be implemented into any existing LSCM. I will also present recent results of combining ISM with two-photon excitation, which is important for deep-tissue imaging of e.g. neuronal tissue, and for performing non-linear coherent microscopy such as second-harmonic generation. A second method which I will present is concerned with achieving nanometer resolution along the optical axis. It is called Metal Induced Energy Transfer or MIET and is based on the fact that, when placing a fluorescent molecule close to a metal, its fluorescence properties change dramatically. In particular, one observes a strongly modified lifetime of its excited state (Purcell effect). This coupling between an excited emitter and a metal film is strongly dependent on the emitter’s distance from the metal. We have used this effect for mapping the basal membrane of live cells with an axial accuracy of ~3 nm. The method is easy to implement and does not require any change to a conventional fluorescence lifetime microscope; it can be applied to any biological system of interest, and is compatible with most other super-resolution microscopy techniques which enhance the lateral resolution of imaging. Moreover, it is even applicable to localizing individual molecules, thus offering the prospect of three-dimensional single-molecule localization microscopy with nanometer isotropic resolution for structural biology.

Prof. Zhen Huang, Department of Chemistry and Department of Biology Georgia State University USA

Dr. Alexander Wlodawer, NIH-USA Center for Cancer Research National Cancer Institute

Special Seminar

Dr. Jawdat Al-Bassam, University of California

Joint Seminar- Organic Chemistry & Structural Biology

Prof. Nasri Nesnas, Department of Chemistry Florida Institute of Technology

Vision is inarguably the most dependable of the five senses. The retina contains light sensing protein receptors (rhodopsins) that incorporate a small polyene molecule derivative of vitamin A, known as 11-cis-retinal. Major clues on understanding the visual cycle have been established through the design of variations of the vitamin A light absorbing molecule, some of which will be presented. A detailed understanding of the inner workings of rhodopsin is not only critical from the stand point of solving mysteries of visual diseases, like Age-related Macular Degeneration (the leading cause of blindness), but also serves as a well established model for elucidating the mechanism of other G-protein coupled receptors (GPCRs). Furthermore, we show that the value of light absorbing molecules expands beyond vision and can be used to trigger neurons thereby aiding the delineation of complex neural networks.

Dr.. Dan Some, Wyatt

Conventional analytical size exclusion chromatography (SEC), often used to determine the solution molecular weight of proteins, is subject to inherent limitations and errors. Multi-angle light scattering (MALS) is a first-principles technique for determining the molar mass and size of macromolecules and nanoparticles in solution, independently of conformation. In combination with SEC, MALS overcomes these obstacles to characterize the biophysical properties of proteins and other biomolecules, including molecular weight, size, native oligomeric state, dynamic equilibria and degradation products. This seminar will present the failure modes of analytical SEC, fundamentals of SEC-MALS and examples of applications to a variety of proteins including IgG, insulin, glycoproteins, membrane proteins and protein complexes as well as viruses and virus-like particles. It will touch on the importance of protein quality control for reproducible science and provide a glimpse into how MALS can analyze complicated protein-protein interactions.

Dr. Benjamin Palmer , Dept. of Structural Biology WIS

Prof. Masha Niv, The Institute of Biochemistry, Food Science and Nutrition, The Robert H Smith Faculty of Agriculture, Food and Environment, The Hebrew University

The bitter taste sensation is elicited by molecules of widely varying chemical structure (http://bitterdb.agri.huji.ac.il/1) and prevents consumption of poisons, many of which are thought to be bitter. The bitter tastants are recognized by bitter taste receptors (TAS2Rs), a subfamily of GPCRs2. Some of the receptors are orphan, or have few known ligands, while others can be activated by numerous, structurally dissimilar compounds3. Furthermore, some compounds are selective towards a single TAS2R, while others activate multiple TAS2Rs. We show that TAS2R-promiscuous and TAS2R-selective bitter molecules differ in size, globularity, and other properties, and develop a selectivity predictor. Selective TAS2Rs are activated by promiscuous compounds, which are anyway recognized by additional TAS2Rs. Thus, unique ligands, that may have been the evolutionary driving force for the development of selective TAS2Rs, still need to be unraveled4. BitterPredict is a new machine-learning based bitterness prediction tool (Dagan-Wiener et al, in revision). It predicts 70% of FDA-approved drugs, but less than 40% of toxic compounds, to be bitter. Additionally, bitter compounds have higher LD50 values (indicating less toxicity) than toxic compounds, challenging the paradigm "bitterness signals toxicity". Interestingly, bitter mouth-rinse leads to lower PANAS mood scores and the effect depends on perceiving the solution as bitter, raising further questions about bitterness in the context of food consumption5. In summary, we explore the selectivity of bitter compounds towards their receptors, and show that the bitterness-toxicity overlap is partial. This supports the idea that activation of bitter taste receptors, which are expressed both orally and extra-orally, has physiological roles beyond alerting against poisons. [1] Wiener, A., Shudler, M., Levit, A., and Niv, M. Y. (2012) BitterDB: a database of bitter compounds, Nucleic acids research 40, D413-419. [2] Di Pizio, A., and Niv, M. Y. (2014) Computational Studies of Smell and Taste Receptors, Israel Journal of Chemistry 54, 1205-1218. [3] Levit, A., Nowak, S., Peters, M., Wiener, A., Meyerhof, W., Behrens, M., and Niv, M. Y. (2014) The bitter pill: clinical drugs that activate the human bitter taste receptor TAS2R14, Faseb J 28, 1181-1197. [4] Di Pizio, A., and Niv, M. Y. (2015) Promiscuity and selectivity of bitter molecules and their receptors, Bioorg Med Chem 23, 4082-4091. [5] Dubovski, N., Ert, E., and Niv, M. Y. (2017) Bitter mouth-rinse affects emotions, Food Quality and Preference 60, 154-164.

Special Departmental Seminar

Prof. Pierre Goloubinoff, University of Lausanne

Prof.Meytal Landau, Technion

Michal Shemesh, WIS Departments of Structural Biology and Molecular Cell Biology

Dr. Renee Vancraenenbroeck , Dr. Hagen Hofmann’s group

Dr. Ronen Gabizon, California Institute for Quantitative Biosciences, University of California, Berkeley

Transcription elongation by RNA polymerase (RNAP) is a complex process involving binding of nucleotides, conformational changes, catalytic steps, and translocation on the DNA template. The processive elongation is interspersed with transcriptional pauses, which play critical roles in coordinating transcription with processes such as translation, splicing and DNA repair. While many mechanisms contributing to pausing have been characterized, it is not clear how transcriptional dynamics of RNA polymerase change at pause sites, and how those dynamics lead to the formation of various paused states. I will present high-resolution optical tweezers experiments in which we characterize the transcription of individual E. coli RNA polymerase molecules through repeating templates. Combining the assay with novel methods of data analysis, we were able to separately investigate the pausing dynamics at different sites for pauses as short as 100 msec, and test how these dynamics are affected by applied force, backtracking and RNA structure formation. Our experiments revealed that: 1. Multiple mechanisms act in synergy to promote pausing in a site-specific manner; 2. RNA structure interacts primarily with the pretranslocated state of RNAP and can both promote or prevent pausing; 3. Backtracked pause states are formed in a site-specific manner and can only be accessed from preexisting paused states. In the second part of the talk I will discuss the application of optical tweezers towards characterizing the stepping behavior of RNA polymerase during active elongation. Individual base-pair steps (~ 3.4 Å) have been observed before in optical tweezers assays but only anecdotally and for short segments of transcription traces. By combining an ultra-high resolution optical tweezers system with a Large-state-space Hidden Markov Model step finding algorithm, we are now able to obtain for the first time full, extended molecular trajectories of RNAP with single base-pair resolution.

Dr. Ramanujan Hegde , Sir John C. Kendrew Memorial Lecture Cambridge UK

2017 Sir John C. Kendrew Memorial Lecture

Dr. Ramanujan Hegde , group leader MRC Laboratory of Molecular Biology

Dr. Zvi Hayouka, HUJI

Special Seminar

Prof. Barry Honig, Colombia University

Special Seminar

Jendrik Schöppe, University of Zurich

Dr. Franziska Zosel, University of Zurich

Nir Funt, Master thesis defense

Dr. Boris Brumshtein, Dept. Chemistry and Biochemistry UCLA

Dr. Julia Shifman, Department of Biological Chemistry Hebrew University

Dr. Alexander Rouvinski, Faculty of Medicine The Hebrew University

Keren Kahil , M.Sc. student of Prof. Lia Addadi and Prof. Steve Weiner Department of Structural Biology

Dr. Sharon Ruthstein, BIU

Dr. Eyal Nir, Department of Chemistry BGU

Dr. Julia Mahamid, Department of Molecular Structural Biology Max Planck Institute of Biochemistry Germany

Prof. Elisha Haas, Head - Biophysics Program BIU

Prof. David Ron, University of Cambridge

Dr. Moran Shalev-Benami, Department of Structural Biology WIS

Prof. Etana Padan, Dept. of Biological Chemistry Hebrew University

Dr. Grzegorz Wieczorek & Dr.Dorota Niedzialek, Institute of Biochemistry and Biophysics, Polish Academy of Science And International Institute of Molecular and Cell Biology

Prof. Assaf Friedler, Institute of Chemistry Hebrew University

Prof. Binghe Wang , Department of Chemistry Georgia State University

Dr. Ran Friedman, Linnaeus University Sweden

Prof. Pralay Mitra, Department of Computer Science & Engineering Indian Institute of Technology, Kharagpur

Dvir Gur,

Student Seminar

Netta Vidavsky, Ph.D student of Prof. Steve Weiner & Prof. Lia Addadi

Dr. Dana Reichmann, Department of Biological Chemistry The Hebrew University of Jerusalem

Prof. Ilya Finkelstein, Department of Molecular Biosciences & ICMB University of Texas at Austin

Prof. Cynthia Wolberger, Department of Biophysics and Biophysical Chemistry Johns Hopkins University School of Medicine

Sir John C. Kendrew Memorial Lecture

Prof. James Wells , Departments of Pharmaceutical Chemistry and Cellular & Molecular Pharmacology, University of California at San Francisco, CA, USA

Special Joint Seminar Organic Chemistry & Structural Biology - Prof. William D. Lubell

Prof. William D. Lubell, Department of Chemistry University of Montréal Canada

Prof. David Avnir, The Institute of Chemistry, Hebrew University

Dr. Yuval Ebenstein, Department of Chemical Physics, Tel Aviv University

Student Seminar -Thesis defense

Anat Akiva, Ph.D student of Prof. Steve Weiner & Prof. Lia Addadi

Prof. Amir Aharoni, Department of Life Sciences Ben Gurion University

Prof. Lynn Kamerlin, Department of Cell and Molecular Biology (ICM) Uppsala University, Sweden

Dr. Adi Stern,

Dr. Eyal Arbeli, Department of Chemistry Ben Gurion University

Prof. Jose-Maria Carazo, National Center of Biotechnology Madrid

Biosynthesis of 2-thioglucose in BE-7585A

Prof. Hung-wen Liu, University of Texas at Austin, Austin

Dr. Mariusz Jaremko, The Max Planck Institute for Biophysical Chemistry Göttingen, Germany

Dr. Zbyszek Dauter, Head, Synchrotron Radiation Research Section Center for Cancer Research National Cancer Institute

Dr. Lukasz Jaremko, The Max Planck Institute for Biophysical Chemistry Göttingen, Germany

Dr. Niv Papo, Department of Biotechnology Engineering Faculty of Engineering Sciences Ben-Gurion University of the Negev

Dr. Yariv Wine, Department of Molecular Microbiology and Biotechnology Tel-Aviv University

Dr. Gil Goobes, Bar Ilan University

Dr. Vered Padler-Karavani, Laboratory of Glycoimmunology Department of Cell Research and Immunology Tel Aviv University

Prof. Roy Bar-Ziv, Department of Materials and Interfaces WIS

Dr. Gabriel A. Frank , Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, NIH

Dr. Tanmay Bharat , MRC

Prof. Cherif Matta, Dept. of Chemistry & Physics Mount Saint Vincent University

Dr. Itamar Kass, Monash University Melbourne, Australia

Dr. Tzviya Zeev-Ben-Mordehai,

Dr. Oksana Degtjarik,

Prof. Joerg Enderlein , Georg-August-University Göttingen

Prof. Arne Elofsson, Science for Life Laboratory Stockholm University

Dr. Nir Ben-Tal, Tel Aviv University

Dr. Lina Malinauskaite, University of Oxford

Dr. Natalie Elia, Ben-Gurion University of the Negev

Kirstin Eisenhauer , Ruhr-University Bochum, Germany

Dr.Yael Mandel-Gutfreund, Faculty of Biology, the Technion

Dr. Yael Mandel-Gutfreund, Faculty of Biology, Technion

Dr. Amir Goldbourt, School of Chemistry Tel Aviv University

Prof. Adrian Goldman, Chair in Membrane Biology The Astbury Centre for Structural Molecular Biology University of Leeds Leeds, UK

Prof. Dmitrij Frishman , Technische Universität München

Prof. Todd Yeates, Department of Chemistry and Biochemistry UCLA

Dr. Chen Davidovich, Department of Chemistry & Biochemistry University of Colorado U.S.A

Prof. Jorg Langowski, German Cancer Research Center (DKFZ)

Dr. David Lukatsky, BGU

Dr. Asher Schmidt , Faculty of Chemistry Technion

Dr. Akram Alian , Faculty of Biology Technion

Margarita Kovtanyuk , M.Sc. student of Prof. Steve Weiner & Prof. Lia Addadi

Margarita Kovtanyuk , M.Sc. student of Prof. Steve Weiner & Prof. Lia Addadi

Dr. Dmitry Veprintsev, Laboratory of Biomolecular Research Paul Scherrer Institut Switzerland

Dr. Dina Schneidman, University of California

Dr.Yarden Opatowsky, Structural Biology Lab BIU

Dr. Rina Rosenzweig, Department of Biology University of Toronto

Prof. Mark Safro, Department of Structural Biology WIS

Dr. Jordan Chill, Department of Chemistry BIU

We think of proteins as ensembles of several mutually-interconverting conformations, and therefore protein 'structure' actually refers to a weighted representation of all conformers contributing to protein behavior. Less intuitive yet very important is the fact that the biological function of proteins depends sometimes upon elusive minor conformers that might be overlooked by a superficial static view. This realization has pushed bio-NMR, a leading solution-based structural method, to the forefront of efforts to identify and, if possible, actually 'see' lowly-populated conformations. The ability of high-resolution NMR to follow and characterize these nearly invisible unsung heroes of protein function will be demonstrated using three case-studies from our research group, (i) intrinsically disordered proteins that challenge the fundamental structure-function dogma, (ii) an under-appreciated pH-dependent oligomerization domain, and (iii) inhibition of a potassium channel by a marine toxin. Together these examples highlight the versatility of solution NMR in illuminating the molecular basis of biological functions involving protein conformational flexibility.