- Protein Structure and Dynamics
- Biochemical Analysis and Sensing Techniques
- Bacterial Genetics and Biotechnology
- RNA and protein synthesis mechanisms
- Ion Transport and Channel Regulation
- Trace Elements in Health
- Spectroscopy and Quantum Chemical Studies
- Amino Acid Enzymes and Metabolism
- Plant-Microbe Interactions and Immunity
- DNA and Nucleic Acid Chemistry
- Drug Transport and Resistance Mechanisms
- Plant pathogens and resistance mechanisms
- Regulation of Appetite and Obesity
- Genomics and Phylogenetic Studies
- Lipid Membrane Structure and Behavior
- Plant Pathogenic Bacteria Studies
- Photosynthetic Processes and Mechanisms
- Microbial Metabolic Engineering and Bioproduction
- Photoreceptor and optogenetics research
- Bacterial biofilms and quorum sensing
- Enzyme Structure and Function
- Cellular transport and secretion
- Fungal and yeast genetics research
- Machine Learning in Bioinformatics
- Clostridium difficile and Clostridium perfringens research
Tel Aviv University
2015-2024
Abstract The ConSurf web‐sever for the analysis of proteins, RNA, and DNA provides a quick accurate estimate per‐site evolutionary rate among homologues. reveals functionally important regions, such as catalytic ligand‐binding sites, which often evolve slowly. Since last report in 2016, has been improved multiple ways. It now user‐friendly interface that makes it easier to perform visualize results. Evolutionary rates are calculated based on set homologous sequences, collected using hidden...
Patterns observed by examining the evolutionary relationships among proteins of common origin can reveal structural and functional importance specific residue positions. In particular, amino acids that are highly conserved (i.e., their positions evolve at a slower rate than other positions) particularly likely to be biological importance, for example, ligand binding. ConSurf is bioinformatics tool accurately estimating each position in protein family. Here we introduce new release...
In search of Botrytis cinerea cell death-inducing proteins, we found a xyloglucanase (BcXYG1) that induced strong necrosis and resistance response in dicot plants. Expression the BcXYG1 gene was strongly during first 12 h post inoculation, analysis disease dynamics using PathTrack showed B. strain overexpressing produced early local necrosis, supporting role as an factor. The activity not necessary for induction plant resistance, mutant lacking enzymatic retained both functions. Residues two...
Crh proteins catalyze crosslinking of chitin and glucan polymers in fungal cell walls. Here, we show that the BcCrh1 protein from phytopathogenic fungus Botrytis cinerea acts as a cytoplasmic effector elicitor plant defense. is localized vacuoles endoplasmic reticulum during saprophytic growth. However, upon infection, accumulates infection cushions; it then secreted to apoplast translocated into cells, where induces death defense responses. Two regions 53 35 amino acids are sufficient for...
Cation/proton antiporters (CPAs) play a major role in maintaining living cells' homeostasis. CPAs are commonly divided into two main groups, CPA1 and CPA2, further characterized by phenotypes: ion selectivity electrogenicity. However, tracing the evolutionary relationships of these transporters is challenging because high diversity within CPAs. Here, we conduct comprehensive analysis 6537 representative CPAs, describing full complexity their phylogeny, revealing sequence motif that appears...
Photosystem I is defined as plastocyanin-ferredoxin oxidoreductase. Taking advantage of genetic engineering, kinetic analyses and cryo-EM, our data provide novel mechanistic insights into binding electron transfer between PSI Pc. Structural at 2.74 Å resolution reveals strong hydrophobic interactions in the plant PSI-Pc ternary complex, leading to exclusion water molecules from PsaA-PsaB/Pc interface once complex forms. Upon oxidation Pc, a slight tilt bound oxidized Pc allows accommodate...
Significance The principal Na + /H antiporter of Escherichia coli (Ec-NhaA) is the best-characterized pH-regulated exchangers that control cellular and H homeostasis, human homologues are potentially important drug targets. Identification essential components NhaA vital to understanding function protein has implications for evolution design. Ec-NhaA 12 helices, 2 which (VI VII) absent from growing number secondary transporters share unique structural fold. Mutants deleted helices VI VII,...
The Homo sapiens Na + /H antiporter NHA2 ( SLC9B2 ) transports or Li in exchange for protons across cell membranes, and its dysfunction results various pathologies. activity of Hs is specifically inhibited by the flavonoid phloretin. Using bioinformatic modeling, we predicted two amino acids (R177 S178) as being important binding phloretin to molecule. Functional expression Saccharomyces cerevisiae site‐directed mutagenesis revealed that while R177T mutation resulted an was less sensitive...
There is ongoing debate regarding the mechanism through which cation/proton antiporters (CPAs), like
All extant life forms require trace transition metals (e.g., Fe2/3+, Cu1/2+, and Mn2+) to survive. However, as these are environmentally scarce, organisms have evolved sophisticated metal uptake machineries. In bacteria, high-affinity import of is predominantly mediated by ABC transporters. During bacterial infection, sequestration the host further limits availability ions, accordingly, transporters (importers) key virulence determinants. structure-function relationships not been fully...
The human Na+ /H+ antiporter NHA2 (SLC9B2) transports or Li+ across the plasma membrane in exchange for protons, and is implicated various pathologies. It a 537 amino acids protein with an 82 residues long hydrophilic cytoplasmic N-terminus followed by transmembrane part comprising 14 helices. We optimized functional expression of HsNHA2 salt-sensitive Saccharomyces cerevisiae strain characterized vivo set mutated truncated versions terms their substrate specificity, transport activity,...
Erv14, a conserved cargo receptor of COPII vesicles, helps the proper trafficking many but not all transporters to yeast plasma membrane, for example, three out five alkali-metal-cation in Saccharomyces cerevisiae. Among them, Nha1 cation/proton antiporter, which participates cell cation and pH homeostasis, is large membrane protein (985 aa) possessing long hydrophilic C-terminus (552 containing six regions (C1-C6) with unknown function. A short version, lacking almost entire C-terminus,...
The Escherichia coli yobA-yebZ-yebY (AZY) operon encodes the proteins YobA, YebZ, and YebY. YobA YebZ are homologs of CopC periplasmic copper-binding protein CopD putative copper importer, respectively, whereas YebY belongs to uncharacterized Domain Unknown Function 2511 family. Despite numerous studies E. homeostasis existence AZY in a range bacteria, operon's their functional roles have not been explored. In this study, we present first biochemical proteins. Biochemical characterization...
Abstract Crh proteins catalyze crosslinking of chitin and glucan polymers in the fugal cell wall. We revealed a novel unexpected role Botrytis cinerea BcCrh1 as cytoplasmic effector elicitor plant defense. During saprophytic growth protein is localized vacuoles ER. Upon infection accumulates to high levels cushions, it then secreted apoplast translocated into cells, where induces death defense responses. Two regions 53 35 amino acids were found sufficient for uptake induction, respectively....
The opportunistic fungus Aspergillus fumigatus is the primary invasive mold pathogen in humans, and responsible for an estimated 200,000 yearly deaths worldwide. Most fatalities occur immunocompromised patients who lack cellular humoral defenses necessary to halt pathogen's advance, primarily lungs. One of responses used by macrophages counteract fungal infection accumulation high phagolysosomal Cu levels destroy ingested pathogens. A. responds activating expression crpA, which encodes a Cu+...
Cation/proton antiporters (CPAs) regulate cells' salt concentration and pH. Their malfunction is associated with a range of human pathologies, yet only handful CPA-targeting therapeutics are presently in clinical development. Here, we discuss how recently published mammalian protein structures emerging computational technologies may help to bridge this gap.
Abstract The human Na + /H antiporter NHA2 ( SLC9B2 ) transports or Li across the plasma membrane in exchange for protons, and is implicated various pathologies. It a 537 amino acids protein with an 82 residues long hydrophilic cytoplasmic N-terminus followed by transmembrane part comprising 14 helices. We optimized functional expression of Hs salt-sensitive Saccharomyces cerevisiae strain characterized set mutated truncated versions terms their substrate specificity, transport activity,...
Abstract Photosystem I is defined as plastocyanin-ferredoxin oxidoreductase. Taking advantage of genetic engineering, kinetic analyses and cryo-EM, our data provide novel mechanistic insights into binding electron transfer between PSI Pc. Structural at 2.74 Å resolution reveals strong hydrophobic interactions in the plant PSI-Pc ternary complex, leading to exclusion water molecules from PsaA-PsaB / Pc interface once complex forms. Upon oxidation Pc, a slight tilt bound oxidized allows...