A5050606685- Protein Structure and Dynamics
- Enzyme Structure and Function
- RNA and protein synthesis mechanisms
- Diffusion and Search Dynamics
- Bacteriophages and microbial interactions
- Microtubule and mitosis dynamics
- RNA Research and Splicing
- Mass Spectrometry Techniques and Applications
- Photosynthetic Processes and Mechanisms
- DNA and Nucleic Acid Chemistry
- Cardiomyopathy and Myosin Studies
- Advanced Neuroimaging Techniques and Applications
- Carbohydrate Chemistry and Synthesis
- Lipid Membrane Structure and Behavior
- Glycosylation and Glycoproteins Research
- Stochastic processes and statistical mechanics
- Ubiquitin and proteasome pathways
- Heat shock proteins research
- Monoclonal and Polyclonal Antibodies Research
- Galectins and Cancer Biology
Weizmann Institute of Science
2018-2023
Hebrew University of Jerusalem
2014
The respiratory and intestinal tracts are exposed to physical biological hazards accompanying the intake of air food. Likewise, vasculature is threatened by inflammation trauma. Mucin glycoproteins related von Willebrand factor guard vulnerable cell layers in these diverse systems. Colon mucins additionally house feed gut microbiome. Here, we present an integrated structural analysis mucin MUC2. Our findings reveal shared mechanism which complex macromolecules responsible for blood clotting,...
In eukaryotes, many DNA/RNA-binding proteins possess intrinsically disordered regions (IDRs) with large negative charge, some of which involve a consecutive sequence aspartate (D) or glutamate (E) residues. We refer to them as D/E repeats. The functional role repeats is not well understood, though are known cause autoinhibition through intramolecular electrostatic interaction domains. this work, we investigated the impacts on target DNA search kinetics for high-mobility group box 1 (HMGB1)...
Replication protein A (RPA) plays a critical role in all eukaryotic DNA processing involving single-stranded (ssDNA). Contrary to the notion that RPA provides solely inert protection transiently formed ssDNA, RPA-ssDNA complex acts as dynamic unit. Here, we studied diffusion of along 60 nt ssDNA using coarse-grained model which ssDNA-RPA interface was modeled by both aromatic and electrostatic interactions. Our study direct evidence bulge formation during RPA. Bulges can form at few sites...
Microtubules (MTs) are essential components of the eukaryotic cytoskeleton that serve as "highways" for intracellular trafficking. In addition to well-known active transport cargo by motor proteins, many MT-binding proteins seem adopt diffusional motility a transportation mechanism. However, because limited spatial resolution current experimental techniques, detailed mechanism protein diffusion has not been elucidated. particular, precise role tubulin tails and tail modifications in process...
DNA-binding proteins rely on linear diffusion along the longitudinal DNA axis, supported by their nonspecific electrostatic affinity for DNA, to search target recognition sites. One may therefore expect that ability engage in is universal all proteins, with detailed biophysical characteristics of differing between depending structures and functions. key question whether mechanism defined translation coupled rotation, a often termed sliding. We conduct coarse-grained atomistic molecular...
This work describes a new role of intrinsically disordered regions in regulating the oligomeric state and thermodynamic stability proteins.
Predicting the effect of a single point mutation on protein thermodynamic stability (ΔΔG) is an ongoing challenge with high relevance for both fundamental and applicable aspects science. Drawbacks that limit predictive power prediction tools include lack representations explicit energetic terms unfolded state. Using coarse-grained simulations analytical modeling analysis, we found involves breaking long-range contacts may lead to increase in state entropy, which can overall destabilization...
Abstract Thermodynamic stability is an important property of proteins that linked to many the trade‐offs characterize a protein molecule and therefore its function. Designing with desired complicated task given intrinsic trade‐off between enthalpy entropy which applies for both folded unfolded states. Traditionally, manipulated by point mutations regulate state enthalpy. In some cases, has also been means drastically restrict conformational dynamics such as engineering disulfide bonds. this...
Many mutations that cause familial hypercholesterolemia localize to ligand-binding domain 5 (LA5) of the low-density lipoprotein receptor, motivating investigation folding and misfolding this small, disulfide-rich, calcium-binding domain. LA5 is known involve non-native disulfide isomers, yet these intermediates have not been structurally characterized. To provide insight into intermediates, we used nuclear magnetic resonance (NMR) follow in real time. We demonstrate misfolded or partially...
Many proteins have intrinsically disordered regions (IDRs), which are often characterized by a high fraction of charged residues with polyampholytic (i.e., mixed charge) or polyelectrolytic uniform characteristics. Polyelectrolytic IDRs include consecutive positively Lys Arg (K/R repeats) negatively Asp Glu (D/E repeats). In previous research, D/E repeats were found to be about five times longer than K/R and much more common in eukaryotes. Within these repeats, preference is observed for E...