A5058535146- Ubiquitin and proteasome pathways
- Enzyme Structure and Function
- Endoplasmic Reticulum Stress and Disease
- DNA and Nucleic Acid Chemistry
- Autophagy in Disease and Therapy
- RNA and protein synthesis mechanisms
- Peptidase Inhibition and Analysis
- Advanced Proteomics Techniques and Applications
- Bacterial Genetics and Biotechnology
- Advanced biosensing and bioanalysis techniques
- Glycosylation and Glycoproteins Research
- DNA Repair Mechanisms
Weizmann Institute of Science
2018-2023
Abundant and essential motifs, such as phosphate-binding loops (P-loops), are presumed to be the seeds of modern enzymes. The Walker-A P-loop is absolutely in NTPase enzymes, mediating binding, transfer terminal phosphate groups NTPs. However, function depends on many additional active-site residues placed throughout protein’s scaffold. Can motifs P-loops confer a simpler context? We applied phylogenetic analysis that yielded sequence logo putative ancestral element: β-strand connected an...
Abstract Controlled degradation of proteins is necessary for ensuring their abundance and sustaining a healthy accurately functioning proteome. One the routes involves uncapped 20S proteasome, which cleaves with partially unfolded region, including those that are damaged or contain intrinsically disordered regions. This route tightly controlled by recently discovered family named Catalytic Core Regulators (CCRs). Here, we show CCRs function through an allosteric mechanism, coupling physical...
Ortholog protein complexes are responsible for equivalent functions in different organisms. However, during evolution, each organism adapts to meet its physiological needs and the environmental challenges imposed by niche. This selection pressure leads structural diversity complexes, which often difficult specify, especially absence of high-resolution structures. Here, we describe a multilevel experimental approach based on native mass spectrometry (MS) tools elucidating preservation...
Aims: The protein degradation machinery plays a critical role in the maintenance of cellular homeostasis, preventing accumulation damaged or misfolded proteins and controlling levels regulatory proteins. 20S proteasome machinery, which predominates during oxidative stress, is able to cleave any with partially unfolded region, however, uncontrolled myriad potential substrates improbable. This study aimed identify characterize mechanism that controls proteasome-mediated degradation. Results:...
The P-loop Walker A motif underlies hundreds of essential enzyme families that bind nucleotide triphosphates (NTPs) and mediate phosphoryl transfer (P-loop NTPases), including the earliest DNA/RNA helicases, translocases, recombinases. What were primordial precursors these enzymes? Could large complex proteins emerge from simple polypeptides? Previously, we showed P-loops embedded in βα repeat NTPs but also, unexpectedly so, ssDNA RNA. Here, extend beyond purely biophysical function ligand...
Abstract The P-loop Walker A motif underlies hundreds of essential enzyme families that bind nucleotide triphosphates (NTPs) and mediate phosphoryl transfer (P-loop NTPases), including the earliest DNA/RNA helicases, translocases recombinases. What were primordial precursors these enzymes? Could large complex proteins emerge from simple polypeptides? Previously, we showed P-loops embedded in βα repeat NTPs, but also, unexpectedly so, ssDNA RNA. Here, extend beyond purely biophysical function...
<p>Ortholog protein complexes are responsible for equivalent functions in different organisms. However, during evolution, each organism adapts to meet its physiological needs and the environmental challenges imposed by niche. This selection pressure leads structural diversity complexes, which often difficult specify, especially absence of high-resolution structures. Here, we describe a multi-level experimental approach based on native mass spectrometry (MS) tools elucidating...
Abstract The protein degradation machinery plays a critical role in the maintenance of cellular homeostasis, preventing accumulation damaged or misfolded proteins and controlling levels regulatory proteins. 20S proteasome is able to cleave any with partially unfolded region, however uncontrolled myriad potential substrates improbable. Thus, there must exist mechanism control mediated degradation. Here we have discovered family regulators, named Catalytic Core Regulators (CCRs). They...
Ortholog protein complexes are responsible for equivalent functions in different organisms. However, during evolution, each organism adapts to meet its physiological needs and the environmental challenges imposed by niche. This selection pressure leads structural diversity complexes, which often difficult specify, especially absence of high-resolution structures. Here, we describe a multi-level experimental approach based on native mass spectrometry (MS) tools elucidating preservation...