A5026217419- Protein Kinase Regulation and GTPase Signaling
- Enzyme Structure and Function
- Receptor Mechanisms and Signaling
- Protein Structure and Dynamics
- Neurobiology and Insect Physiology Research
- Biochemical and Molecular Research
- Cellular transport and secretion
- Glycosylation and Glycoproteins Research
- Cancer-related gene regulation
- Endoplasmic Reticulum Stress and Disease
- Cell Adhesion Molecules Research
- Amino Acid Enzymes and Metabolism
- Photoreceptor and optogenetics research
- Melanoma and MAPK Pathways
- Microbial Metabolic Engineering and Bioproduction
- Retinal Development and Disorders
- Monoclonal and Polyclonal Antibodies Research
- Olfactory and Sensory Function Studies
- Bioinformatics and Genomic Networks
- Immune cells in cancer
- Neuropeptides and Animal Physiology
- Metabolism, Diabetes, and Cancer
- Marine Invertebrate Physiology and Ecology
- Pancreatic function and diabetes
- Genetic Associations and Epidemiology
University of Haifa
2013-2025
Carmel (Israel)
2013
Duke Medical Center
2007-2012
Duke University Hospital
2008-2011
Smith-Kettlewell Eye Research Institute
2007
Columbia University
2006-2007
Hebrew University of Jerusalem
2000-2003
University of Notre Dame
2003
Abstract It is often assumed that in the Protein Data Bank (PDB), two proteins with similar sequences will also have structures. Accordingly, it has proved useful to develop subsets of PDB from which “redundant” structures been removed, based on a sequence‐based criterion for similarity. Similarly, when predicting protein structure using homology modeling, if template modeling target sequence selected by alone, this implicitly assumes all sequence‐similar templates are equivalent. Here, we...
Members of the Receptor Tyrosine Kinase (RTK) superfamily are regulators cellular signaling, playing essential roles in growth, differentiation, and survival. Dysregulation RTKs leads to diseases such as cancer, diabetes, inflammatory disorders, making them important therapeutic targets. Despite extensive research on RTKs, structural diversity evolutionary relationships across not fully understood. Here, we systematically compared conservation divergence among 245 extracellular domains from...
The heterotrimeric G protein transducin is a key component of the vertebrate phototransduction cascade. Transducin peripherally attached to membranes rod outer segment, where it interacts with other proteins at membrane-cytosol interface. However, upon sustained activation by light, dissociated G(t)alpha and Gbeta(1)gamma(1) subunits translocate from segment parts cell. Here we used computational approach analyze interaction strength its acidic lipid bilayers, as well range orientations that...
G protein-coupled receptors (GPCRs) are intensively studied due to their therapeutic potential as drug targets. Members of this large family transmembrane receptor proteins mediate signal transduction in diverse cell types and play key roles human physiology health. In 2013 the research consortium GLISTEN (COST Action CM1207) was founded with goal harnessing substantial growth knowledge GPCR structure dynamics push forward development molecular modulators function. The success GLISTEN,...
Abstract Analysis of 501 melanoma exomes revealed RGS7 , which encodes a GTPase-accelerating protein (GAP), to be tumor-suppressor gene. was mutated in 11% melanomas and found harbor three recurrent mutations (p.R44C, p.E383K p.R416Q). Structural modeling the most common mutation (p.R44C) predicted that it destabilizes due loss an H-bond salt bridge network between position serine aspartic acid residues at positions 58 as 61, respectively. We experimentally confirmed this prediction showing...
Fly photoreceptors are polarized cells, each of which has an extended interface between its cell body and the light-signaling compartment, rhabdomere. Upon intense illumination, rhabdomeric calcium concentration reaches millimolar levels that would be toxic if Ca(2+) diffusion rhabdomere was not robustly attenuated. Yet, it is clear how such effective attenuation obtained. Here we show homeostasis in photoreceptor relies on protein calphotin. This unique functions as immobile buffer...
Chemical communication is fundamental for the operation of insect societies. Their diverse vocabulary chemical signals requires a correspondingly set chemosensory receptors. Insect olfactory receptors (ORs) are largest family The OR characterized by frequent expansions subfamilies, in which duplicated ORs may adapt to detect new through positive selection on their amino acid sequence. Ants an extreme example with ∼400 per genome-the highest number insects. Presumably, this reflects increased...
In a family of proteins, often the three-dimensional structure has been experimentally determined only for one member or few members family. Homology modeling can be used to model structures all other and thus allow comparison these structures. This approach was applied heterotrimeric G proteins that require anchorage plasma membrane properly interact with membrane-bound receptors downstream effectors. Lipid modification by palmitoylation is fundamental contributor this localization, but...
Specific amino acids within RGS proteins may encode specificity toward G protein α subunits.
Enhanced activation of the signaling pathways that mediate differentiation mononuclear monocytes into osteoclasts is an underlying cause several bone diseases and metastasis. In particular, dysregulation overexpression macrophage colony-stimulating factor (M-CSF) its c-FMS tyrosine kinase receptor, proteins are essential for osteoclast differentiation, known to promote metastasis osteoporosis, making both ligand receptor attractive targets therapeutic intervention. With this aim in mind, our...
Regulators of G protein signaling (RGS) proteins inactivate Gα subunits, thereby controlling protein-coupled networks. Among all RGS proteins, RGS2 is unique in interacting only with the Gαq but not Gαi subfamily. Previous studies suggested that this specificity determined by domain and, particular, three RGS2-specific residues lead to a mode interaction This was further proposed act through contacts GTPase domain. Here, we combined energy calculations and activity measurements determine...
Abstract Homomers are prevalent in bacterial proteomes, particularly among core metabolic enzymes. Homomerization is often key to function and regulation, interfaces that facilitate the formation of homomeric enzymes subject intense evolutionary change. However, our understanding molecular mechanisms drive variation complexes still lacking. How diversification protein linked functional regulation structural integrity complexes? To address this question, we studied quaternary structure...