Structure of a Complete ATP Synthase Dimer Reveals the Molecular Basis of Inner Mitochondrial Membrane Morphology

Mol Cell. 2016 Aug 4;63(3):445-56. doi: 10.1016/j.molcel.2016.05.037. Epub 2016 Jun 30.

Abstract

We determined the structure of a complete, dimeric F1Fo-ATP synthase from yeast Yarrowia lipolytica mitochondria by a combination of cryo-EM and X-ray crystallography. The final structure resolves 58 of the 60 dimer subunits. Horizontal helices of subunit a in Fo wrap around the c-ring rotor, and a total of six vertical helices assigned to subunits a, b, f, i, and 8 span the membrane. Subunit 8 (A6L in human) is an evolutionary derivative of the bacterial b subunit. On the lumenal membrane surface, subunit f establishes direct contact between the two monomers. Comparison with a cryo-EM map of the F1Fo monomer identifies subunits e and g at the lateral dimer interface. They do not form dimer contacts but enable dimer formation by inducing a strong membrane curvature of ∼100°. Our structure explains the structural basis of cristae formation in mitochondria, a landmark signature of eukaryotic cell morphology.

Keywords: F(1)F(o)-ATP synthase dimer; X-ray crystallography; bioenergetics; cryoelectron microscopy; inner membrane morphology; membrane protein complex; mitochondria; rotary ATPase mechanism; yeast Yarrowia lipolytica.

Publication types

  • Video-Audio Media

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Catalysis
  • Cryoelectron Microscopy
  • Crystallography, X-Ray
  • Fungal Proteins / chemistry*
  • Fungal Proteins / metabolism
  • Fungal Proteins / ultrastructure
  • Mitochondria / enzymology*
  • Mitochondria / ultrastructure
  • Mitochondrial Membranes / enzymology*
  • Mitochondrial Membranes / ultrastructure
  • Mitochondrial Proton-Translocating ATPases / chemistry*
  • Mitochondrial Proton-Translocating ATPases / metabolism
  • Mitochondrial Proton-Translocating ATPases / ultrastructure
  • Models, Molecular
  • Protein Conformation, alpha-Helical
  • Protein Multimerization
  • Protein Subunits
  • Structure-Activity Relationship
  • Yarrowia / enzymology*
  • Yarrowia / ultrastructure

Substances

  • Fungal Proteins
  • Protein Subunits
  • Adenosine Triphosphate
  • F1F0-ATP synthase
  • Mitochondrial Proton-Translocating ATPases