Crystal structure of mitochondrial respiratory membrane protein complex II

Cell. 2005 Jul 1;121(7):1043-57. doi: 10.1016/j.cell.2005.05.025.


The mitochondrial respiratory Complex II or succinate:ubiquinone oxidoreductase (SQR) is an integral membrane protein complex in both the tricarboxylic acid cycle and aerobic respiration. Here we report the first crystal structure of Complex II from porcine heart at 2.4 A resolution and its complex structure with inhibitors 3-nitropropionate and 2-thenoyltrifluoroacetone (TTFA) at 3.5 A resolution. Complex II is comprised of two hydrophilic proteins, flavoprotein (Fp) and iron-sulfur protein (Ip), and two transmembrane proteins (CybL and CybS), as well as prosthetic groups required for electron transfer from succinate to ubiquinone. The structure correlates the protein environments around prosthetic groups with their unique midpoint redox potentials. Two ubiquinone binding sites are discussed and elucidated by TTFA binding. The Complex II structure provides a bona fide model for study of the mitochondrial respiratory system and human mitochondrial diseases related to mutations in this complex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites / physiology
  • Cell Respiration / physiology*
  • Crystallography, X-Ray
  • Electron Transport / physiology*
  • Electron Transport Complex II / chemistry*
  • Electron Transport Complex II / metabolism
  • Enzyme Inhibitors / pharmacology
  • Flavoproteins / chemistry
  • Intracellular Membranes / metabolism*
  • Iron-Sulfur Proteins / chemistry
  • Membrane Proteins / chemistry
  • Mitochondria / metabolism*
  • Models, Molecular
  • Molecular Sequence Data
  • Oxidation-Reduction
  • Protein Structure, Tertiary / physiology
  • Protein Subunits / chemistry
  • Sequence Homology, Amino Acid
  • Succinic Acid / metabolism
  • Sus scrofa
  • Ubiquinone / metabolism


  • Enzyme Inhibitors
  • Flavoproteins
  • Iron-Sulfur Proteins
  • Membrane Proteins
  • Protein Subunits
  • Ubiquinone
  • Succinic Acid
  • Electron Transport Complex II

Associated data

  • PDB/1ZOY
  • PDB/1ZP0