A5043274215- Receptor Mechanisms and Signaling
- Neuropeptides and Animal Physiology
- Monoclonal and Polyclonal Antibodies Research
- Mass Spectrometry Techniques and Applications
- Complement system in diseases
- Chemokine receptors and signaling
- Lipid Membrane Structure and Behavior
- T-cell and B-cell Immunology
- Protein Structure and Dynamics
- Protein Kinase Regulation and GTPase Signaling
- Gait Recognition and Analysis
- Magnetic and Electromagnetic Effects
- Infrared Target Detection Methodologies
- Plant Growth and Agriculture Techniques
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Adenosine and Purinergic Signaling
- Immunotherapy and Immune Responses
- Microbial Metabolic Engineering and Bioproduction
- Insect Pest Control Strategies
- Enzyme Catalysis and Immobilization
- Video Surveillance and Tracking Methods
- biodegradable polymer synthesis and properties
- Salmonella and Campylobacter epidemiology
- Computational Drug Discovery Methods
- interferon and immune responses
Indian Institute of Technology Kanpur
2022-2025
Shri Venkateshwara University
2024
Academy of Scientific and Innovative Research
2018
Institute of Genomics and Integrative Biology
2018
Council of Scientific and Industrial Research
2018
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...
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...
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...
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...
Abstract Agonist-induced interaction of G protein-coupled receptors (GPCRs) with β-arrestins (βarrs) is a critical mechanism that regulates the spatio-temporal pattern receptor localization and downstream signaling. While underlying governing GPCR-βarr primarily conserved involves activation phosphorylation, there are several examples receptor-specific fine-tuning βarr-mediated functional outcomes. Considering key contribution conformational plasticity βarrs in driving responses, it...
Abstract β-arrestins are multifunctional proteins that critically involved in regulating spatio-temporal aspects of GPCR signaling. The interaction with GPCRs is typically conceptualized terms receptor activation and phosphorylation primarily the carboxyl-terminus. Interestingly however, there several harbor majority sites their 3 rd intracellular loop (ICL3) instead carboxyl-terminus but still robustly engage β-arrestins. Moreover, 7TMRs now characterized as intrinsically-biased,...
Surveillance has a great importance at all times whether war time or peace time. The aim of our paper is to make convertible robot which will work in the three media's (i.e., air, water, land).During flight mode, it detach itself from rest body reduce its weight during easy for flight. A camera be mounted on capture images. image can also interrupted by some noise rectified using Image Processing. . This concept used real application UAV, UAVs are basically images and videos through...
Abstract Activation of the complement cascade is a critical part our innate immune response against invading pathogens, and it operates in concerted fashion with antibodies phagocytic cells towards clearance pathogens. The peptide C5a, generated during activation cascade, potent inflammatory molecule, increased levels C5a are implicated multiple disorders including advanced stages COVID-19 pathophysiology. proximal step C5a-mediated cellular physiological responses its interaction two...
The present investigation was conducted at Fruit Research Farm, Department of Horticulture, AAI-DU, Allahabad during August 2002 to December with the objective determining effect different levels EMS on seed germination, sensitivity, and seedling growth papaya. experiment laid out in a Completely Randomized Design (CRD) comprising five treatments i.e. Control (2 h soaking) (To), 0.2% (T 1 ), 0.4% 2 0.6% 3 ) 0.8% 4 replications. Papaya cv. Farm Selection-1 taken for this study. Observations...
Abstract Chemokine receptors constitute an important subfamily of G protein-coupled (GPCRs), and they are critically involved in a broad range immune response mechanisms. Ligand promiscuity among these makes them interesting target to explore novel aspects biased agonism. Here, we comprehensively characterize two chemokine namely, CXCR4 CXCR7, which share common agonist (CXCL12), terms their G-protein coupling, β-arrestin (βarr) recruitment, contribution GRKs, ERK1/2 MAP kinase activation....
Abstract The Hydroxycarboxylic acid receptor 2 (HCA2), also known as the niacin or GPR109A, is a prototypical G protein-coupled that plays central role in inhibition of lipolytic and atherogenic activities our body. Interestingly, GPR109A activation results vasodilation linked to side-effect flushing associated with dyslipidemia drugs such niacin. This continues be key target for developing novel pharmacophores lead compounds potential therapeutics minimized response, however, lack...
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Abstract Agonist-induced phosphorylation of G protein-coupled receptors (GPCRs) is a key determinant for the binding and activation multifunctional regulatory proteins known as β-arrestins (βarrs). Although primary sequence pattern GPCRs are poorly conserved, downstream functional responses mediated by βarrs such receptor desensitization, endocytosis signaling broadly applicable across GPCRs. A conserved principle βarr activation, if any, upon their interaction with different harboring...
Abstract The complement cascade is an integral part of innate immunity, and it plays a crucial role in our body’s immune response including combating microbial infections. Activation the results generation multiple peptide fragments, which C3a C5a are potent anaphylatoxins. binds activates G protein-coupled receptor (GPCR) known as C3aR while two distinct receptors namely C5aR1 C5aR2. Our current understanding recognition by their corresponding limited primarily to biochemical studies,...