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TitleStructures of the otopetrin proton channels Otop1 and Otop3.
Journal, issue, pagesNat Struct Mol Biol, Vol. 26, Issue 6, Page 518-525, Year 2019
Publish dateJun 3, 2019
AuthorsKei Saotome / Bochuan Teng / Che Chun Alex Tsui / Wen-Hsin Lee / Yu-Hsiang Tu / Joshua P Kaplan / Mark S P Sansom / Emily R Liman / Andrew B Ward /
PubMed AbstractOtopetrins (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 ...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.
External linksNat Struct Mol Biol / PubMed:31160780 / PubMed Central
MethodsEM (single particle)
Resolution2.98 - 3.32 Å
Structure data

9360

6nf4

EMDB-9360, PDB-6nf4:
Structure of zebrafish Otop1 in nanodiscs
Method: EM (single particle) / Resolution: 2.98 Å

9361

6nf6

EMDB-9361, PDB-6nf6:
Structure of chicken Otop3 in nanodiscs
Method: EM (single particle) / Resolution: 3.32 Å

Chemicals

ChemComp-Y01:
CHOLESTEROL HEMISUCCINATE

ChemComp-CLR:
CHOLESTEROL

Source
  • danio rerio (zebrafish)
  • gallus gallus (chicken)
KeywordsMEMBRANE PROTEIN / Proton channel / Otopetrin

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