6aei

Cryo-EM structure of the receptor-activated TRPC5 ion channel

Loading... Status: waiting for Mol* initialization Structural highlights 6aei is a 4 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.89Å Ligands: LPP, NA, Y01 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function TRPC5_MOUSE Thought to form a receptor-activated non-selective calcium permeant cation channel. Probably is operated by a phosphatidylinositol second messenger system activated by receptor tyrosine kinases or G-protein coupled receptors. Has also been shown to be calcium-selective. May also be activated by intracellular calcium store depletion. Publication Abstract from PubMed The transient receptor potential canonical subfamily member 5 (TRPC5), one of seven mammalian TRPC members, is a nonselective calcium-permeant cation channel. TRPC5 is of considerable interest as a drug target in the treatment of progressive kidney disease, depression, and anxiety. Here, we present the 2.8-A resolution cryo-electron microscopy (cryo-EM) structure of the mouse TRPC5 (mTRPC5) homotetramer. Comparison of the TRPC5 structure to previously determined structures of other TRPC and TRP channels reveals differences in the extracellular pore domain and in the length of the S3 helix. The disulfide bond at the extracellular side of the pore and a preceding small loop are essential elements for its proper function. This high-resolution structure of mTRPC5, combined with electrophysiology and mutagenesis, provides insight into the lipid modulation and gating mechanisms of the TRPC family of ion channels. Cryo-EM structure of TRPC5 at 2.8-A resolution reveals unique and conserved structural elements essential for channel function.,Duan J, Li J, Chen GL, Ge Y, Liu J, Xie K, Peng X, Zhou W, Zhong J, Zhang Y, Xu J, Xue C, Liang B, Zhu L, Liu W, Zhang C, Tian XL, Wang J, Clapham DE, Zeng B, Li Z, Zhang J Sci Adv. 2019 Jul 24;5(7):eaaw7935. doi: 10.1126/sciadv.aaw7935. eCollection 2019, Jul. PMID:31355338 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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