6l93 | pdb_00006l93
X-ray structure of the ligand-free human TRPV1 ankyrin repeat domain
Structural highlights
FunctionTRPV1_HUMAN Ligand-activated non-selective calcium permeant cation channel involved in detection of noxious chemical and thermal stimuli. Seems to mediate proton influx and may be involved in intracellular acidosis in nociceptive neurons. Involved in mediation of inflammatory pain and hyperalgesia. Sensitized by a phosphatidylinositol second messenger system activated by receptor tyrosine kinases, which involves PKC isozymes and PCL. Activation by vanilloids, like capsaicin, and temperatures higher than 42 degrees Celsius, exhibits a time- and Ca(2+)-dependent outward rectification, followed by a long-lasting refractory state. Mild extracellular acidic pH (6.5) potentiates channel activation by noxious heat and vanilloids, whereas acidic conditions (pH <6) directly activate the channel. Can be activated by endogenous compounds, including 12-hydroperoxytetraenoic acid and bradykinin. Acts as ionotropic endocannabinoid receptor with central neuromodulatory effects. Triggers a form of long-term depression (TRPV1-LTD) mediated by the endocannabinoid anandamine in the hippocampus and nucleus accumbens by affecting AMPA receptors endocytosis.[UniProtKB:O35433][1] [2] [3] [4] Publication Abstract from PubMedTRPV1, a member of the transient receptor potential (TRP) channels family, has been found to be involved in redox sensing. The crystal structure of the human TRPV1 ankyrin-repeat domain (TRPV1-ARD) was determined at 4.5 A resolution under nonreducing conditions. This is the first report of the crystal structure of a ligand-free form of TRPV1-ARD and in particular of the human homologue. The structure showed a unique conformation in finger loop 3 near Cys258, which is most likely to be involved in inter-subunit disulfide-bond formation. Also, in human TRPV1-ARD it was possible for solvent to access Cys258. This structural feature might be related to the high sensitivity of human TRPV1 to oxidants. ESI-MS revealed that Cys258 did not form an S-OH functionality even under nonreducing conditions. Structure determination of the human TRPV1 ankyrin-repeat domain under nonreducing conditions.,Tanaka M, Hayakawa K, Ogawa N, Kurokawa T, Kitanishi K, Ite K, Matsui T, Mori Y, Unno M Acta Crystallogr F Struct Biol Commun. 2020 Mar 1;76(Pt 3):130-137. doi:, 10.1107/S2053230X20001533. Epub 2020 Mar 2. PMID:32133998[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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