Protein-Membrane Interactions and Protein-Protein Recognition within the Cell Membrane: Mode of Action of Membrane Proteins Involved in Cell Permeation in Infectious Diseases
Protein-membrane interactions and protein-protein recognition within the membrane milieu are of fundamental importance to fully comprehend a wide range of cellular processes in all organisms. About 40% of all genes in the mammalian genome transcribe membrane proteins, which can be classified into three major groups:
- water-soluble peptides and proteins that undergo substantial conformational changes to allow them to interact with and insert into the membrane (e.g. peptide and protein toxins)
- integral membrane proteins that fold into active forms within the membrane (e.g. receptors, ion channels)
- proteins containing both integral parts and water/membrane soluble regions (e.g. envelope proteins of viruses).
The paucity in 3D structures for most membrane proteins, the high complexity of the forces involved, and the technical difficulties present challenging obstacles to overcome before fully understanding biological events within membranes. Using a multidisciplinary approach, which includes peptide chemistry (peptide synthesis and chemical ligation), molecular (protein expression) and cell biology (cells, bacteria and viruses), biophysics, and in vivo studies using animal models, we are studying the three types of membrane proteins, focusing on those involved in infectious diseases.
The distinct advantage in studying this variety of biological systems lies in our ability to extract general rules that underline most types of interactions involved between proteins and membranes. These studies led us to discover and refine mechanisms of action of membrane proteins involved in infectious diseases; namely, microbial and viral infections.
Acknowledgements
- The Harold S. and Harriet B. Brady Professorial Chair in Cancer Research
- Israel Science Foundation
- USA-Israel Binational Agricultural Research and Development Fund (BARD)
- UK-Israel Foundation
- Pasteur- Weizmann
- The Minerva Foundation
- Weizman-Yale
- European Community (EC)
- The Prostate Cancer (former CapCure) Foundation
- The Israel Cancer Association (ICA)
- The Israel Cancer Research Foundation (ICRF)
- PCRF (former UK prostate Cancer Foundation)
Internal Support
- The Estate of Julius and Hanna Rosen
- The Dr. Joseph Cohn Minerva Center for Biomembrane Research
- John Hopkins-Weizmann
- Gutwirth Award
- Horowitz Foundation