Department of Structural Biology
Zippora Shakked, 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. GordonStructures 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 HaranLFER analysis of allosteric transitions in proteins.
Allostery in the structure and function of GroEL and CCT chaperonins.
Analysis of correlated mutations in proteins
The mechanisms of protein-DNA recognition: understanding the driving forces for fast assembly
The effect of post-translational modifications on the biophysics of proteins
The assembly and budding of virions.
- The kinetics and localization of viral budding.
- The surface localization and mobility of the envelope glycoprotein.
- The mechanical properties of the virus particle.
Hearing micromechanics - the mechanical properties of the tectorial membrane
M. Safro
On the Role of Electrostatic Interactions in Formation of Aminoacyl-tRNA Synthetase - tRNA Encounter Complexes
Human, Cytoplasmic and Mitochondrial Phenylalanyl-tRNA Synthetase: Cloning, Expression, 3-D-structure, Complexes with Functional Ligands
M. Safro, Dr. N. MoorFidelity of the Genetic Code Translation: Editing Activity of Phenylalanyl-tRNA synthetase
Amino Acids Biogenesis, Evolution of the Genetic Code and Aminoacyl-tRNA Synthetases
I. Sagi
Structural -Dynamic studies of Metalloenzymes and Protein-Nucleic Acid Interactions.
Our research covers a wide range of areas with the common themes of dynamic structure-function investigations. The principle areas of investigation are mechanism of action of metalloenzymes and protein-nucleic acid interactions. Our objective is to study
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
Structure 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.
3D structural studies of halotolerant proteins from unicellular alga Dunaliella.
Application of ultra rapid X-ray diffraction methods to study the enzymatic mechanism of AChE in real time.
3-D structure analysis and prediction of protein structures; and design and construction of a large object oriented relational data base for 3D structures of biological macromolecules found in the protein data bank.
S. Weiner
Archaeological science: minerals and molecules in the sediments of the archaeological record.
Structure - mechanical function relations in mineralized tissues (bone and teeth).
S. Weiner, H.D. WagnerBiomineralization: mechanisms of mineral formation and growth in biology.
S. Weiner, L. SddadiProtein biosynthesis
Ribosomal mechanisms
Antibiotics targeting ribosomes