Solution structure and elevator mechanism of the membrane electron transporter CcdA

Nat Struct Mol Biol. 2018 Feb;25(2):163-169. doi: 10.1038/s41594-018-0022-z. Epub 2018 Jan 29.

Abstract

Membrane oxidoreductase CcdA plays a central role in supplying reducing equivalents from the bacterial cytoplasm to the envelope. It transports electrons across the membrane using a single pair of cysteines by a mechanism that has not yet been elucidated. Here we report an NMR structure of the Thermus thermophilus CcdA (TtCcdA) in an oxidized and outward-facing state. CcdA consists of two inverted structural repeats of three transmembrane helices (2 × 3-TM). We computationally modeled and experimentally validated an inward-facing state, which suggests that CcdA uses an elevator-type movement to shuttle the reactive cysteines across the membrane. CcdA belongs to the LysE superfamily, and thus its structure may be relevant to other LysE clan transporters. Structure comparisons of CcdA, semiSWEET, Pnu, and major facilitator superfamily (MFS) transporters provide insights into membrane transporter architecture and mechanism.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Archaeoglobus fulgidus
  • Bacterial Proteins / chemistry*
  • Cell Membrane / enzymology
  • Cross-Linking Reagents / chemistry
  • Cysteine / chemistry
  • Magnetic Resonance Spectroscopy
  • Membrane Transport Proteins / chemistry
  • Models, Molecular
  • Oxidation-Reduction
  • Oxidoreductases / chemistry
  • Protein Binding
  • Protein Structure, Secondary
  • Protein Transport
  • Solvents / chemistry
  • Thermus thermophilus / enzymology*

Substances

  • Bacterial Proteins
  • CcdA protein, Bacteria
  • Cross-Linking Reagents
  • Membrane Transport Proteins
  • Solvents
  • Oxidoreductases
  • Cysteine