Methanogenic heterodisulfide reductase (HdrABC-MvhAGD) uses two noncubane [4Fe-4S] clusters for reduction

Science. 2017 Aug 18;357(6352):699-703. doi: 10.1126/science.aan0425.

Abstract

In methanogenic archaea, the carbon dioxide (CO2) fixation and methane-forming steps are linked through the heterodisulfide reductase (HdrABC)-[NiFe]-hydrogenase (MvhAGD) complex that uses flavin-based electron bifurcation to reduce ferredoxin and the heterodisulfide of coenzymes M and B. Here, we present the structure of the native heterododecameric HdrABC-MvhAGD complex at 2.15-angstrom resolution. HdrB contains two noncubane [4Fe-4S] clusters composed of fused [3Fe-4S]-[2Fe-2S] units sharing 1 iron (Fe) and 1 sulfur (S), which were coordinated at the CCG motifs. Soaking experiments showed that the heterodisulfide is clamped between the two noncubane [4Fe-4S] clusters and homolytically cleaved, forming coenzyme M and B bound to each iron. Coenzymes are consecutively released upon one-by-one electron transfer. The HdrABC-MvhAGD atomic model serves as a structural template for numerous HdrABC homologs involved in diverse microbial metabolic pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Archaeal Proteins / chemistry*
  • Archaeal Proteins / ultrastructure
  • Coenzymes / chemistry
  • Coenzymes / ultrastructure
  • Crystallography, X-Ray
  • Electron Transport
  • Ferredoxins / chemistry
  • Iron / chemistry
  • Iron-Sulfur Proteins / chemistry*
  • Iron-Sulfur Proteins / ultrastructure
  • Metabolic Networks and Pathways
  • Methanococcaceae / enzymology*
  • Oxidation-Reduction
  • Oxidoreductases / chemistry*
  • Oxidoreductases / ultrastructure
  • Protein Domains
  • Sulfur / chemistry

Substances

  • Archaeal Proteins
  • Coenzymes
  • Ferredoxins
  • Iron-Sulfur Proteins
  • Sulfur
  • Iron
  • Oxidoreductases
  • heterodisulfide reductase