Prokaryotic assembly factors for the attachment of flavin to complex II

Biochim Biophys Acta. 2013 May;1827(5):637-47. doi: 10.1016/j.bbabio.2012.09.003. Epub 2012 Sep 14.

Abstract

Complex II (also known as Succinate dehydrogenase or Succinate-ubiquinone oxidoreductase) is an important respiratory enzyme that participates in both the tricarboxylic acid cycle and electron transport chain. Complex II consists of four subunits including a catalytic flavoprotein (SdhA), an iron-sulphur subunit (SdhB) and two hydrophobic membrane anchors (SdhC and SdhD). Complex II also contains a number of redox cofactors including haem, Fe-S clusters and FAD, which mediate electron transfer from succinate oxidation to the reduction of the mobile electron carrier ubiquinone. The flavin cofactor FAD is an important redox cofactor found in many proteins that participate in oxidation/reduction reactions. FAD is predominantly bound non-covalently to flavoproteins, with only a small percentage of flavoproteins, such as complex II, binding FAD covalently. Aside from a few examples, the mechanisms of flavin attachment have been a relatively unexplored area. This review will discuss the FAD cofactor and the mechanisms used by flavoproteins to covalently bind FAD. Particular focus is placed on the attachment of FAD to complex II with an emphasis on SdhE (a DUF339/SDH5 protein previously termed YgfY), the first protein identified as an assembly factor for FAD attachment to flavoproteins in prokaryotes. The molecular details of SdhE-dependent flavinylation of complex II are discussed and comparisons are made to known cofactor chaperones. Furthermore, an evolutionary hypothesis is proposed to explain the distribution of SdhE homologues in bacterial and eukaryotic species. Mechanisms for regulating SdhE function and how this may be linked to complex II function in different bacterial species are also discussed. This article is part of a Special Issue entitled: Respiratory complex II: Role in cellular physiology and disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Sequence
  • Bacteria / genetics
  • Bacteria / metabolism*
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Electron Transport Complex II / chemistry
  • Electron Transport Complex II / genetics
  • Electron Transport Complex II / metabolism*
  • Flavin-Adenine Dinucleotide / chemistry
  • Flavin-Adenine Dinucleotide / metabolism*
  • Models, Molecular
  • Molecular Sequence Data
  • Molecular Structure
  • Protein Binding
  • Protein Structure, Tertiary
  • Protein Subunits / chemistry
  • Protein Subunits / genetics
  • Protein Subunits / metabolism
  • Sequence Homology, Amino Acid

Substances

  • Bacterial Proteins
  • Protein Subunits
  • respiratory complex II
  • Flavin-Adenine Dinucleotide
  • Electron Transport Complex II