A5102745331- Ion Channels and Receptors
- Ion channel regulation and function
- Plant Stress Responses and Tolerance
- Neuroscience and Neuropharmacology Research
- Receptor Mechanisms and Signaling
- Photoreceptor and optogenetics research
- Enzyme Structure and Function
- Magnetic and Electromagnetic Effects
- Neurobiology and Insect Physiology Research
- Biochemical effects in animals
- Hearing, Cochlea, Tinnitus, Genetics
- Bioactive Compounds and Antitumor Agents
- Molecular Sensors and Ion Detection
- Mass Spectrometry Techniques and Applications
- Protein Structure and Dynamics
- Connexins and lens biology
- Drug Transport and Resistance Mechanisms
- Nicotinic Acetylcholine Receptors Study
- Freezing and Crystallization Processes
- Bacterial Genetics and Biotechnology
- Nitrogen and Sulfur Effects on Brassica
- Calcium signaling and nucleotide metabolism
- Cancer therapeutics and mechanisms
- Protein Kinase Regulation and GTPase Signaling
- Healthcare and Venom Research
Indian Institute of Technology Kanpur
2020-2023
Columbia University
2016-2020
Council of Scientific and Industrial Research
2012-2017
Institute of Microbial Technology
2014-2017
Guy's Hospital
1993
Abstract Transient receptor potential (TRP) channels are involved in various physiological processes, including sensory transduction. The TRP channel TRPV6 mediates calcium uptake epithelia and its expression is dramatically increased numerous types of cancer. inhibitors suppress tumor growth, but the molecular mechanism inhibition remains unknown. Here, we present crystal cryo-EM structures human rat bound to 2-aminoethoxydiphenyl borate (2-APB), a inhibitor modulator channels. 2-APB binds...
Cryo-EM structures of the epithelial calcium channel TRPV6-calmodulin complex reveal a mechanism Ca 2+ -induced inactivation.
Not your typical GPCR Among the large family of G protein–coupled receptors (GPCRs) are many orphans, so called because their signaling reactions remain poorly understood. these is GPR158 which highly expressed in nervous system and implicated processes from cognition to memory mood. Patil et al . determined a high-resolution structure alone bound regulator protein (RGS) complex. has an unusual dimerization mode with extensive interaction interface that locks it conformation likely prevents...
Abstract Tetrameric ion channels have either swapped or non-swapped arrangements of the S1–S4 and pore domains. Here we show that mutations in transmembrane domain TRPV6 can result conversion from a domain-swapped to fold. These results reveal structural determinants swapping raise possibility single channel subtype fold into arrangement vivo , affecting its function normal disease states.
Abstract Algae produce the largest amount of oxygen on earth and are invaluable for human nutrition biomedicine, as well chemical industry, energy production agriculture. The mechanisms by which algae can detect respond to changes in their environments rely membrane receptors, including TRP ion channels. Here we present a 3.5-Å resolution cryo-EM structure transient receptor potential (TRP) channel crTRP1 from alga Chlamydomonas reinhardtii that opens response increased temperature is...
Small-molecule piperazine derivatives mimic inactivation by calmodulin to selectively and potently block TRPV6 channels.
GPR155 is a polymodal lysosomal membrane transceptor comprising both transporter domain and GPCR domain, predominantly expressed in brain. facilitates cholesterol-dependent mTORC1 signaling implicated neurological disorders like Huntington disease. The likely does not bind extracellular ligands canonically, the functional relationship between domains remains unclear. Here, we report first structures of monomeric human two distinct dimers, revealing an inward-open inactivated with unique...
We present evidence that the neurite out-growth stimulated by binding of Thy-1 antibodies to PC12 cells is mediated calcium influx through both N- and L-type channels. cultured on a noncellular substratum in presence NGF, or cellular absence responded soluble antibody extending longer neurites. The response required bivalent could be blocked removing from surface with phosphatidylinositol specific phospholipase C. also reducing extracellular 0.25 mM, antagonists L- N-type Additionally, fully...
Precise synapse formation is essential for normal functioning of the nervous system. Retinal photoreceptors establish selective contacts with bipolar cells, aligning neurotransmitter release apparatus postsynaptic signaling cascades. This involves transsynaptic assembly between dystroglycan-dystrophin complex on photoreceptor and orphan receptor GPR179 cell, which mediated by extracellular matrix protein pikachurin (also known as EGFLAM). plays a critical role in synaptic organization signal...
AMPA receptors, which shape excitatory postsynaptic currents and are directly involved in overactivation of synaptic function during seizures, represent a well-accepted target for anti-epileptic drugs. Trans-4-butylcyclohexane carboxylic acid (4-BCCA) has emerged as new promising drug several vitro vivo seizure models, but the mechanism its action remained unknown. The purpose this study is to characterize structure dynamics 4-BCCA interaction with receptors.We studied molecular receptor...
Abstract AMPA subtype ionotropic glutamate receptors (iGluRs) mediate the majority of fast neurotransmission across excitatory synapses in central nervous system. Each receptor is composed four multi-domain subunits that are organized into layers two amino-terminal domain (ATD) dimers, ligand-binding (LBD) transmembrane domains and carboxy-terminal domains. We introduced cysteine substitutions at intersubunit interfaces subunit GluA2 confirmed substituted crosslink formation by SDS-PAGE. The...
Binding of substrates into the active site, often through complementarity shapes and charges, is central to specificity an enzyme. In many cases, substrate binding induces conformational changes in promoting specific interactions between them. contrast, non-substrates either fail bind or do not induce requisite upon thus no catalysis occurs. principle, both lock key induced-fit can provide this study, we present interesting case where cofactor pre-tunes site geometry recognize only cognate...
Fad35R from Mycobacterium tuberculosis binds to the promoter site of Fad35 operon and its DNA binding activities are reduced in presence tetracycline palmitoyl-CoA. We resolved crystal structure using single-wavelength anomalous diffraction method (SAD). comprises canonical domain (DBD) ligand (LBD), but displays several distinct structural features. Two recognition helices two monomers homodimer separated by ~ 48 Å core triangle-shaped cavities well exposed solvent. Structural comparison...
Dug1p, a M20 family metallopeptidase and human orthologue of carnosinase, hydrolyzes Cys-Gly dipeptide, the last step glutathione (GSH) degradation in Saccharomyces cerevisiae. Molecular bases peptide recognition by Dug1p other peptidases remain unclear absence structural information about enzyme–peptide complexes. We report crystal structure at 2.55 Å resolution complex with Gly-Cys dipeptide two Zn2+ ions. The is trapped tunnel-like active site; its C-terminus held residues S1′ binding...
Abstract Tetrameric ion channels have either swapped or non-swapped arrangements of the S1-S4 and pore domains. Here we show that mutations in transmembrane domain TRPV6 can result conversion from a domain-swapped to fold. These results reveal structural determinants swapping raise possibility single channel subtype fold into arrangement vivo , affecting its function normal disease states.