Structure of the c(10) ring of the yeast mitochondrial ATP synthase in the open conformation

Nat Struct Mol Biol. 2012 Apr 15;19(5):485-91, S1. doi: 10.1038/nsmb.2284.

Abstract

The proton pore of the F(1)F(o) ATP synthase consists of a ring of c subunits, which rotates, driven by downhill proton diffusion across the membrane. An essential carboxylate side chain in each subunit provides a proton-binding site. In all the structures of c-rings reported to date, these sites are in a closed, ion-locked state. Structures are here presented of the c(10) ring from Saccharomyces cerevisiae determined at pH 8.3, 6.1 and 5.5, at resolutions of 2.0 Å, 2.5 Å and 2.0 Å, respectively. The overall structure of this mitochondrial c-ring is similar to known homologs, except that the essential carboxylate, Glu59, adopts an open extended conformation. Molecular dynamics simulations reveal that opening of the essential carboxylate is a consequence of the amphiphilic nature of the crystallization buffer. We propose that this new structure represents the functionally open form of the c subunit, which facilitates proton loading and release.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Binding Sites
  • Crystallography, X-Ray
  • Mitochondrial Proton-Translocating ATPases / chemistry*
  • Molecular Dynamics Simulation*
  • Protein Conformation
  • Protein Subunits / chemistry
  • Protons
  • Saccharomyces cerevisiae / chemistry
  • Saccharomyces cerevisiae / enzymology*

Substances

  • Protein Subunits
  • Protons
  • F1F0-ATP synthase
  • Mitochondrial Proton-Translocating ATPases

Associated data

  • PDB/3U2F
  • PDB/3U2Y
  • PDB/3U32
  • PDB/3UD0