6nf6

Structure of chicken Otop3 in nanodiscs

Loading... Status: waiting for Mol* initialization Structural highlights 6nf6 is a 2 chain structure with sequence from Chick. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: Y01 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Otopetrins (Otop1-Otop3) comprise one of two known eukaryotic proton-selective channel families. Otop1 is required for otoconia formation and a candidate mammalian sour taste receptor. Here we report cryo-EM structures of zebrafish Otop1 and chicken Otop3 in lipid nanodiscs. The structures reveal a dimeric architecture, with each subunit forming 12 transmembrane helices divided into structurally similar amino (N) and carboxy (C) domains. Cholesterol-like molecules occupy various sites in Otop1 and Otop3 and occlude a central tunnel. In molecular dynamics simulations, hydrophilic vestibules formed by the N and C domains and in the intrasubunit interface between N and C domains form conduits for water entry into the membrane core, suggesting three potential proton conduction pathways. By mutagenesis, we tested the roles of charged residues in each putative permeation pathway. Our results provide a structural basis for understanding selective proton permeation and gating of this conserved family of proton channels. Structures of the otopetrin proton channels Otop1 and Otop3.,Saotome K, Teng B, Tsui CCA, Lee WH, Tu YH, Kaplan JP, Sansom MSP, Liman ER, Ward AB Nat Struct Mol Biol. 2019 Jun;26(6):518-525. doi: 10.1038/s41594-019-0235-9. Epub, 2019 Jun 3. PMID:31160780 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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