Department of Structural Biology
Abraham Minsky, Head
Structural biology is an increasingly important and exciting area. Much of the research in this area at the Weizmann Institute is carried out in the Faculty of Chemistry. Current research projects involve utilization of the main methodologies available for biological structural studies, such as X-ray crystallography, NMR, electron and atomic force microscopies, molecular biology and various other spectroscopic techniques. Modern and sophisticated instrumentational facilities are available, most of which are state-of-the-art. Studies are being performed to determine molecular structures and structure-function relationships in biological macromolecules, such as proteins, DNA and their complexes. Efforts are also directed towards the design of potential drugs. Whole intracellular assemblies and organelles, such as the ribosomes, which contain tens of macromolecules, are being investigated. The powerful techniques of site-directed mutagenesis and thermodynamics are being used together with theoretical analyses to characterize the interactions that stabilize proteins and determine their activity. Antigen-antibody complexes and other protein-protein interactions such as that of interferon with its receptor are being studied by multi-dimensional NMR methods. Biomineralization, i.e. controlled mineral deposition by organisms to form skeletal tissues, is being investigated from the molecular interactions between proteins and crystals to the ultrastructure and properties of the tissue.Antibodies that recognize crystal surfaces and 2-dimensional organized patterns.
- antibody recognition of chiral crystal surfaces
- structure of cholesterol/ceramide monolayer mixtures. Molecular organization of lipid rafts
- Pathological crystallizations. Gout
- antibody recognition of amiloid structures
Mechanisms of crystal nucleation and modulation of crystal growth and properties in biomineralization (bone, mollusk shells, echinoderms).
L. Addadi, S. WeinerMechanism of cell adhesion using crystal substrates.
L. Addadi, B. GeigerThe structure of the V3 loop of the HIV-1 envelope protein gp120 and its interactions with chemokines receptors
J. Anglister, F. NaiderThe structure of the membrane proximal extra-cellular region of HIV-1 gp41 and its role in viral fusion
J. Anglister, F. NaiderNMR structure of alpha Interferon complex with its receptor
J. Anglister, J. PiehlerThe interactions of scorpion toxins with sodium channels and the structures of the channels extra-cellular loops
J. Anglister, M. Gurevitz, D. GordonViral glycoproteins - HIV and others
BBSome structure and function
Structures of retrovirus envelope proteins and mechanisms of retrovirus entry into cells.
Structure and function of proteins that modulate intracellular membrane dynamics.
Origins of disulfide bonds for oxidative protein folding.
Chaperonin-mediated protein folding.
A. Horovitz, Gilad Haran; Maya Schuldiner;Linear free energy relationships (LFER) analysis of allosteric transitions in proteins.
Allostery in the structure and function of GroEL and CCT chaperonins.
A. Horovitz, Keith Willison (Cancer Research Institute, London); Michal Sharon;Analysis of correlated mutations in proteins
A. Horovitz, Ron Unger (Bar Ilan University)The mechanisms of protein-DNA recognition: understanding the driving forces for fast assembly
The biophysics and evolution of post-translational modifications
Cellular organization of biomacromolecules
- High-resolution structural studies of ordered cellular biomacromolecules and of ordered DNA and DNA-protein complexes.
- Packaging and ordered phases of DNA in living systems (bacteria, sperm cells).
- Effects of stress (starvation, drugs, cold-shock) on DNA and protein organization within cells.
Infection cycles of giant viruses
A. Minsky, Michael Rossmann
- DNA translocations within host cells
- Formation and structure of viral factories
Repair of double-strand DNA breaks
- DNA diffusion
- Repair in highly-resistant organisms (e.g. Deinococcus Radiodurans)
Crystal structure and solution studies of DNA oligomers.
Z. Shakked, Donald Crothers (Yale University)
- DNA regulatory elements
- DNA bending by adenine-thymine tracts
Structural and biochemical studies of proteins involved in transcriptional regulation.
- The tumor-suppressor protein p53 and its interaction with DNA and the basal transcription machinery
- The leukemia-related RUNX1(AML1) transcription regulator
X-ray structural analysis and molecular biology studies on proteins from the nervous system, including acetylcholinesterase (AChE), human, torpedo, drosophila, and krait; butyrylcholinesterase; neural cell adhesion proteins with sequence similarity to ACh
J. Sussman, Israel SilmanStructure based drug design studies on AChE and beta-secretase, including studies of complexes with transition state analogs; potential drugs for the treatment of Alzheimer's disease; and snake neurotoxins.
J. Sussman, Israel SilmanApplication of ultra rapid X-ray diffraction methods to study the enzymatic mechanism of AChE in real time.
J. Sussman, Israel SilmanVisualization of 3D Protein Structures via new web based tool Proteopedia
J. Sussman, Jaime Prilusky & Israel Silman3D Structure Fucntions studies of Paraoxonase
J. Sussman, Dan Tawfik & Israel Silman3D Structure Funciton Studies or proteins related to Autism
J. Sussman, Israel Silman3D Structure Funciton of proteins related to Gaucher Disease
J. Sussman, Tony Futerman & Israel SilmanArchaeological science: revealing the microscopic archaeological record
S. Weiner, E. Boaretto, I Finkelstein, A. Maier, R. Shahack-GrossStructure - mechanical function relations in mineralized tissues (bones and teeth) using Optical Metrology.
S. Weiner, Ron ShaharBiomineralization: mechanisms of mineral formation and growth in biology.
S. Weiner, L. Addadi, Irit Sagi, Leeor KronickProtein biosynthesis
Ribosomal mechanisms
Antibiotics targeting ribosomes