A5081786054- Mosquito-borne diseases and control
- Receptor Mechanisms and Signaling
- Phosphodiesterase function and regulation
- Protein Kinase Regulation and GTPase Signaling
- Bacteriophages and microbial interactions
- RNA and protein synthesis mechanisms
- SARS-CoV-2 and COVID-19 Research
- Protein Structure and Dynamics
- Mass Spectrometry Techniques and Applications
- Bacterial Genetics and Biotechnology
- Viral Infections and Vectors
- Plant Virus Research Studies
- Enzyme Structure and Function
- HIV Research and Treatment
- Insect symbiosis and bacterial influences
- Chemical Synthesis and Analysis
- Malaria Research and Control
- Computational Drug Discovery Methods
- Monoclonal and Polyclonal Antibodies Research
- Vibrio bacteria research studies
- Cholinesterase and Neurodegenerative Diseases
- Biochemical and Molecular Research
- Viral Infections and Outbreaks Research
- Amino Acid Enzymes and Metabolism
- Plant Parasitism and Resistance
Sree Chitra Thirunal Institute for Medical Sciences and Technology
2025
Pennsylvania State University
2021-2025
National University of Singapore
2015-2024
Philadelphia University
2021
Center for Disease Dynamics, Economics & Policy
2021
Indian Institute of Science Bangalore
2015
University of California, San Diego
2002-2007
Howard Hughes Medical Institute
1998-2007
University of California, Riverside
2007
San Diego Supercomputer Center
2003
The spike (S) protein is the main handle for SARS-CoV-2 to enter host cells via surface angiotensin-converting enzyme 2 (ACE2) receptors. How ACE2 binding activates proteolysis of S unknown. Here, using amide hydrogen–deuterium exchange mass spectrometry and molecular dynamics simulations, we have mapped S:ACE2 interaction interface uncovered long-range allosteric propagation sites necessary host-mediated protein, critical viral entry. Unexpectedly, enhances at a distal S1/S2 cleavage site...
SARS-CoV-2 emergent variants are characterized by increased viral fitness and each shows multiple mutations predominantly localized to the spike (S) protein. Here, amide hydrogen/deuterium exchange mass spectrometry has been applied track changes in S dynamics from variants. Our results highlight large differences across at two loci with impacts on stability. A significant enhancement stabilization first occurred emergence of D614G followed smaller, progressive subsequent Stabilization...
cAMP and the binding domain (CBD) constitute a ubiquitous regulatory switch that translates an extracellular signal into biological response. The CBD contains α- β-subdomains with to phosphate cassette (PBC) in β-sandwich. major receptors for mammalian cells are subunits (R-subunits) of PKA where catalytic subunit compete same CBD. R-subunits inhibit kinase activity, whereas releases inhibition. Here, we use NMR map at residue resolution cAMP-dependent interaction network CBD-A isoform Iα...
The response regulator SsrB activates expression of genes encoded within and outside a pathogenicity island (SPI-2), which is required for systemic infection Salmonella. binds upstream the sifA, sifB, sseJ effector directly regulates transcription. also relieves gene silencing by nucleoid protein H-NS. Single molecule experiments with magnetic tweezers demonstrated that displaces H-NS from DNA only when it bound in polymerization (stiffening) mode not to bridging mode. Thus, contrast...
Dengue virus serotype 2 (DENV2) alone undergoes structural expansion at 37 °C (associated with host entry), despite high sequence and homology among the four known serotypes. The basis for this differential across strains serotypes is unknown necessitates mapping of dynamics dengue whole viral particles to describe their coordinated motions conformational changes when exposed host-like environments. Here we capture intact two serotypes, DENV1 DENV2, by amide hydrogen/deuterium exchange mass...
ABSTRACT Accumulating evidence indicates a potential role for bacterial lipopolysaccharide (LPS) in the overactivation of immune response during SARS-CoV-2 infection. LPS is recognized by Toll-like receptor 4, mediating proinflammatory effects. We previously reported that directly interacts with spike (S) protein and enhances activities. Using native gel electrophoresis hydrogen–deuterium exchange mass spectrometry, we showed binds to multiple hydrophobic pockets spanning both S1 S2 subunits...
Abstract Background The cyclic nucleotide binding (CNB) domain regulates signaling pathways in both eukaryotes and prokaryotes. In this study, we analyze the evolutionary information embedded genomic sequences to explore diversity of through CNB also how elicits a cellular response upon cAMP. Results Identification classification domains Global Ocean Sampling other protein reveals that they typically are fused wide variety functional domains. have undergone major sequence variation during...
Plants respond rapidly to sudden environmental cues, often responding prior changes in the hormone levels that coordinate these responses. How this is achieved not fully understood. The integrative role of phytohormone jasmonic acid (JA) relies upon plant's ability control JASMONATE ZIM (JAZ) domain-containing repressor proteins. Here, we demonstrate regardless intrinsic JA levels, Small Ubiquitin-like Modifier (SUMO)-conjugated JAZ proteins inhibit receptor CORONATINE INSENSITIVE1 (COI1)...
Hydrogen–deuterium exchange mass spectrometry (HDX-MS) is an established, powerful tool for investigating protein–ligand interactions, protein folding, and dynamics. However, HDX-MS still emergent quality control of biopharmaceuticals establishing dynamic similarity between a biosimilar innovator therapeutic. Because industry will conduct measurements over product lifetime in multiple locations, understanding reproducibility critical. To determine the continuous-labeling, bottom-up...
<title>Abstract</title> The use of extracellular vesicles (EVs) in bone tissue engineering is emerging as a promising alternative strategy to stem cells. For clinical application, EVs must be biomanufactured from suitable source cells, systematically characterized, and validated for their efficacy regeneration. This study focuses on the possibility this translation using vitro methods with rat marrow cells (rBMSCs). Bone was harvested Wistar rats cultured direct adherence method. rBMSCs were...
Structural studies of eukaryotic RNA polymerase II (Pol II) transcription complexes often depend on in vitro assembly by mixing purified Pol with synthetic DNA/RNA scaffolds, recombinant factors, and/or histones, followed stalling at defined positions adding selected nucleotide triphosphate substrates. These have yielded remarkable results for understanding the elongation factors and nucleosome but may fail to represent native conditions. To investigate within metazoan cells, we developed an...
The envelope (E) protein of dengue virus (DENV) is glycosylated at two highly conserved asparagine (N) sites (N67 and N153). role importance these N-linked glycans in DENV pathogenesis has been elusive. Here, we report the critical N153-linked on E preventing antibody-mediated viral clearance. A DENV2 mutant lacking (N153Q mutant) was engineered found to be mildly impaired vitro but drastically attenuated a symptomatic mouse model severe dengue, as evidenced by accelerated In B...
ABSTRACT Engineered recombinant Spike (S) has been invaluable for determining S structure and dynamics is the basis design of most prevalent vaccines. While these vaccines have highly efficacious short-term protection from infection, waned with emergence variants (alpha through omicron). Here we report differences in conformational between native, membrane-embedded full-length S. Our virus-like particle (VLP) model mimics native SARS CoV-2 virion by displaying assembled auxiliary E, M, N...
The SARS-CoV-2 spike glycoprotein binds human epithelial cells and enables infection through a key conformational transition that exposes its receptor binding domain (RBD). Experimental evidence indicates mutations, particularly the early D614G variant, alter rate of this shift, potentially increasing viral infectivity. To investigate how mutations reshape landscape, we conducted extensive weighted ensemble simulations Ancestral, Delta, Omicron BA.1 strains along RBD opening pathway. We...
An important goal after structural genomics is to build up the structures of higher-order protein-protein complexes from individual subunits. Often higher order are difficult obtain by crystallography. We have used an alternative approach in which catalytic (C) subunit and RIalpha regulatory (R) PKA were first subjected computational docking, top 100,000 solutions subsequently filtered based on amide hydrogen/deuterium (H/2H) exchange interface protection data. The resulting set forms...