A5049768801- Receptor Mechanisms and Signaling
- Complement system in diseases
- Monoclonal and Polyclonal Antibodies Research
- Neuropeptides and Animal Physiology
- Protein Structure and Dynamics
- Mass Spectrometry Techniques and Applications
- Chemokine receptors and signaling
- Enzyme Structure and Function
- Animal Nutrition and Physiology
- Silkworms and Sericulture Research
- RNA and protein synthesis mechanisms
- Biochemical and Molecular Research
- Lipid Membrane Structure and Behavior
- Bacteriophages and microbial interactions
- Agricultural Practices and Plant Genetics
- Bacterial Genetics and Biotechnology
- T-cell and B-cell Immunology
- Viral Infections and Immunology Research
- Effects of Environmental Stressors on Livestock
- Alkaline Phosphatase Research Studies
- Social and Economic Development in India
- ATP Synthase and ATPases Research
- Protein Tyrosine Phosphatases
- Pancreatic function and diabetes
- Genetic and phenotypic traits in livestock
Indian Institute of Technology Kanpur
2016-2025
Government of India
2020-2021
Department of Scientific and Industrial Research
2020-2021
Ministry of Science and Technology
2020-2021
Saha Institute of Nuclear Physics
2012-2014
Indian Space Research Organisation
2013
Institute of Crystallography
2013
Central Sericultural Research and Training Institute
2011
Indian Institute of Chemical Biology
1985-2003
University of California, Los Angeles
1997
Agonist-induced GPCR phosphorylation is a key determinant for the binding and activation of β-arrestins (βarrs). However, it not entirely clear how different GPCRs harboring divergent patterns impart converging active conformation on βarrs leading to broadly conserved functional responses such as desensitization, endocytosis, signaling. Here, we present multiple cryo-EM structures activated in complex with distinct derived from carboxyl terminus GPCRs. These help identify P-X-P-P type motif...
β-arrestins (βarrs) are multifunctional proteins involved in signaling and regulation of seven transmembrane receptors (7TMRs), their interaction is driven primarily by agonist-induced receptor activation phosphorylation. Here, we present cryo-electron microscopy structures βarrs either the basal state, activated muscarinic subtype 2 (M2R) through its third intracellular loop, or βarr-biased decoy D6 (D6R). Combined with biochemical, cellular, biophysical experiments, these structural...
Abstract G Protein-coupled receptors (GPCRs) constitute the largest family of cell surface and drug targets. GPCR signalling desensitization is critically regulated by β-arrestins (βarr). GPCR–βarr interaction biphasic where phosphorylated carboxyl terminus GPCRs docks to N-domain βarr first then seven transmembrane core receptor engages with βarr. It currently unknown whether fully engaged complex essential for functional outcomes or partially can also be functionally competent. Here we...
G-protein-coupled receptors (GPCRs), also known as seven transmembrane (7TMRs), typically interact with two distinct signal-transducers, i.e., G proteins and β-arrestins (βarrs). Interestingly, there are some non-canonical 7TMRs that lack protein coupling but βarrs, although an understanding of their transducer preference, downstream signaling, structural mechanism remains elusive. Here, we characterize such 7TMRs, namely, the decoy D6 receptor (D6R) complement C5a subtype 2 (C5aR2), in...
The complement system is a critical part of our innate immune response, and the terminal products this cascade, anaphylatoxins C3a C5a, exert their physiological pathophysiological responses primarily via two GPCRs, C3aR C5aR1. However, molecular mechanism ligand recognition, activation, signaling bias these receptors remains mostly elusive. Here, we present nine cryo-EM structures C5aR1 activated by natural synthetic agonists, which reveal distinct binding pocket topologies provide key...
Abstract The Hydroxycarboxylic acid receptor 2 (HCA2), also known as the niacin or GPR109A, is a prototypical GPCR that plays central role in inhibition of lipolytic and atherogenic activities. Its activation results vasodilation linked to side-effect flushing associated with dyslipidemia drugs such niacin. GPR109A continues be target for developing potential therapeutics minimized response. Here, we present cryo-EM structures complex drugs, acipimox, non-flushing agonists, MK6892 GSK256073,...
Abstract Agonist-induced phosphorylation of G protein-coupled receptors (GPCRs) is a primary determinant β-arrestin (βarr) recruitment and trafficking. For several GPCRs such as the vasopressin receptor subtype 2 (V R), agonist-stimulation first drives translocation βarrs to plasma membrane, followed by endosomal trafficking, which generally considered be orchestrated multiple sites. We have previously shown that mutation single site in V R (i.e., T360A ) results near-complete loss βarr...
Chemokine receptors are critically involved in multiple physiological and pathophysiological processes related to immune response mechanisms. Most chemokine prototypical GPCRs although some also exhibit naturally-encoded signaling-bias toward β-arrestins (βarrs). C-X-C type receptors, namely CXCR3 CXCR7, constitute a pair wherein the former is GPCR while latter exhibits selective coupling βarrs despite sharing common natural agonist: CXCL11. Moreover, CXCR7 recognize small molecule agonists...
The poliovirus-encoded, membrane-associated polypeptide 2C is believed to be required for initiation and elongation of RNA synthesis. We have expressed purified recombinant, histidine-tagged examined its ability bind the first 100 nucleotides poliovirus 5' untranslated region positive strand complementary 3'-terminal negative-strand sequences. Results presented here demonstrate that specifically binds sequences RNA. Since this form a stable cloverleaf structure, number mutations were...
Abstract Selectivity of natural agonists for their cognate receptors is one the hallmarks members GPCR family, and it crucial specificity downstream signal-transduction. However, this selectivity often breaks down in chemokine receptor subfamily, wherein a high degree promiscuity observed with recognizing multiple chemokines binding to receptors. The molecular determinants such striking ligands chemokine-chemokine system remain mostly elusive represent an important knowledge gap our current...
The Duffy antigen receptor is a seven-transmembrane (7TM) protein expressed primarily at the surface of red blood cells and displays strikingly promiscuous binding to multiple inflammatory homeostatic chemokines. It serves as basis group system in humans also acts primary attachment site for malarial parasite Plasmodium vivax pore-forming toxins secreted by Staphylococcus aureus. Here, we comprehensively profile transducer coupling this receptor, discover potential non-canonical signaling...
Transient expression of the poliovirus-encoded protease 2APro in eukaryotic cells results inhibition both cellular transcription and translation. The observed expressing could be due to a primary effect or secondary caused by Because transcriptional activity TATA-binding protein (TBP) is drastically reduced poliovirus-infected cells, we determined if able cleave TBP vitro. We demonstrate here that directly cleaves single tyrosine-glycine bond at position 34 TBP. This cleavage also seen HeLa...
Psu is a capsid decoration protein of bacteriophage P4 and acts as an antiterminator Rho-dependent transcription termination in bacteria. So far, no structures have been reported for the or its homologues. Here, we report first structure solved by Hg(2+) single wavelength anomalous dispersion method, which reveals that exists knotted homodimer kind nature. Each monomer attains novel fold around tight coiled-coil motif. CD spectroscopy engineered disulfide-bridged derivative reveal folds...
The conserved bacterial transcription terminator, Rho, is a potent target for bactericidal agents. Psu, bacteriophage P4 capsid protein, capable of inducing anti-termination to the Rho-dependent termination. Knowledge structural and mechanistic basis this required design peptide-inhibitor(s) Rho from Psu. Using suppressor genetics, cross-linking, protein foot-printing FRET analyses, we describe disordered structure, encompassing 139–153 amino acids as primary docking site Also neighbouring...
Psu, a 20-kD bacteriophage P4 capsid decorating protein moonlights as transcription antiterminator of the Rho-dependent termination. Psu forms specific complex with E.coli Rho protein, and affects latter's ATP-dependent translocase activity along nascent RNA. It unique knotted dimer to take V-shaped structure. The C-terminal helix makes contacts disordered region Rho, encompassing residues 139-153. An energy minimized structural model Rho-Psu reveals that lid over central channel hexamer....
Abstract The Duffy antigen receptor, also known as FY glycoprotein or CD234, is a seven transmembrane protein expressed primarily at the surface of red blood cells, which displays promiscuous binding to multiple chemokines. Not only does it serve basis group system but acts primary attachment site for malarial parasite Plasmodium vivax on erythrocytes and one nucleating receptors pore forming toxins secreted by Staphylococcus aureus . Despite predicted 7TM architecture efficient spectrum...
To improve mulberry foliage productivity, identification of suitable genes related to agronomically important traits in the available germplasm is essential. Twenty-five indigenous accessions representing five different species Morus from seven diverse parts India were evaluated via principal component analysis (PCA) for 22 aboveground and underground morphometric silkworm cocoon yield during 2002–2005 agro-climates Berhampore, West Bengal, India. Significant differences among observed all...
Chaudhuri, K., Banerjee, R., Pandit, B., Mukherjee, A., Das, S., Sengupta, Roychoudury, S. and Bhattacharyya, N. P. Identification of Two Differentially Expressed Mitochondrial Genes in a Methotrexate-Resistant Chinese Hamster Cell Strain Derived from V79 Cells Using RNA Fingerprinting by Arbitrary Primed Polymerase Chain Reaction. Radiat. Res. 160, 77–85 (2003).To identify genes that are differentially expressed methotrexate (MTX)-resistant cell strain designated as M5 exhibits resistance...