A5001283984- Ubiquitin and proteasome pathways
- Protein Structure and Dynamics
- Enzyme Structure and Function
- Glycosylation and Glycoproteins Research
- Advanced NMR Techniques and Applications
- Cancer-related Molecular Pathways
- Peptidase Inhibition and Analysis
- Cancer, Hypoxia, and Metabolism
- Autophagy in Disease and Therapy
- NMR spectroscopy and applications
- Endoplasmic Reticulum Stress and Disease
- RNA and protein synthesis mechanisms
- Protein Kinase Regulation and GTPase Signaling
- Protein Degradation and Inhibitors
- Biochemical and Molecular Research
- Metabolomics and Mass Spectrometry Studies
- Genetics and Neurodevelopmental Disorders
- interferon and immune responses
- Cellular transport and secretion
- Advanced MRI Techniques and Applications
- Cancer-related gene regulation
- Mass Spectrometry Techniques and Applications
- Molecular spectroscopy and chirality
- Hippo pathway signaling and YAP/TAZ
- Mitochondrial Function and Pathology
University of Maryland, College Park
2015-2024
University of Utah
2021
Park University
2015-2021
Frederick National Laboratory for Cancer Research
2020
Tel Aviv University
2020
University of Haifa
2015
Oranim Academic College of Education
2015
Bio-Rad (Israel)
2012
Ben-Gurion University of the Negev
2011
California Institute of Technology
2004-2005
Abstract The Papain-like protease (PLpro) is a domain of multi-functional, non-structural protein 3 coronaviruses. PLpro cleaves viral polyproteins and posttranslational conjugates with poly-ubiquitin protective ISG15, composed two ubiquitin-like (UBL) domains. Across coronaviruses, showed divergent selectivity for recognition cleavage despite sequence conservation. We show that SARS-CoV-2 binds human ISG15 K48-linked di-ubiquitin (K48-Ub 2 ) nanomolar affinity detect alternate...
Diverse cellular events are regulated by post-translational modification of substrate proteins via covalent attachment one or a chain ubiquitin molecules. The outcome (poly)ubiquitination depends upon the specific lysine residues involved in formation polyubiquitin chains. Lys48-linked chains act as universal signal for proteasomal degradation, whereas Lys63-linked several non-degradative processes. Although it has been anticipated that functional diversity between alternatively linked...
To identify previously unknown small molecules that inhibit cell cycle machinery, we performed a chemical genetic screen in Xenopus extracts. One class of inhibitors, termed ubistatins, blocked progression by inhibiting cyclin B proteolysis and inhibited degradation ubiquitinated Sic1 purified proteasomes. Ubistatins the binding substrates to proteasome targeting ubiquitin-ubiquitin interface Lys 48 -linked chains. The same is recognized ubiquitin-chain receptors proteasome, indicating...
Structural analysis of proteins and nucleic acids is complicated by their inherent flexibility, conferred, for example, linkers between contiguous domains. Therefore, the macromolecule needs to be represented an ensemble conformations instead a single conformation. Determining this challenging because experimental data are convoluted average contributions from multiple conformations. As number degrees freedom generally greatly exceeds independent observables, directly deconvolving into...
The magnitude and orientation of the 15N chemical shift anisotropy (CSA) tensors are determined for human ubiquitin in solution from relaxation data at 600, 500, 360 MHz. analysis uses model-independent approach [Fushman, D.; Cowburn, D. J. Am. Chem. Soc. 1998, 120, 7109−10] based on a ratio, η/R2, cross correlation (η) between CSA 15N−1H dipolar interaction rate (R2) transverse relaxation. Since η/R2 ratio does not contain any direct dependence protein dynamics, present is free assumptions...
Polymeric chains made of a small protein ubiquitin act as molecular signals regulating variety cellular processes controlling essentially all aspects eukaryotic biology. Uncovering the mechanisms that allow differently linked polyubiquitin to serve distinct requires ability make these with native connectivity, defined length, linkage composition, and in sufficient quantities. This, however, has been major impediment field. Here, we present robust, efficient, widely accessible method for...