Cryo-EM structure of trimeric Mycobacterium smegmatis succinate dehydrogenase with a membrane-anchor SdhF

Nat Commun. 2020 Aug 25;11(1):4245. doi: 10.1038/s41467-020-18011-9.

Abstract

Diheme-containing succinate:menaquinone oxidoreductases (Sdh) are widespread in Gram-positive bacteria but little is known about the catalytic mechanisms they employ for succinate oxidation by menaquinone. Here, we present the 2.8 Å cryo-electron microscopy structure of a Mycobacterium smegmatis Sdh, which forms a trimer. We identified the membrane-anchored SdhF as a subunit of the complex. The 3 kDa SdhF forms a single transmembrane helix and this helix plays a role in blocking the canonically proximal quinone-binding site. We also identified two distal quinone-binding sites with bound quinones. One distal binding site is formed by neighboring subunits of the complex. Our structure further reveals the electron/proton transfer pathway for succinate oxidation by menaquinone. Moreover, this study provides further structural insights into the physiological significance of a trimeric respiratory complex II. The structure of the menaquinone binding site could provide a framework for the development of Sdh-selective anti-mycobacterial drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / metabolism
  • Binding Sites
  • Catalysis
  • Cryoelectron Microscopy
  • Electron Transport
  • Models, Molecular
  • Multienzyme Complexes / chemistry
  • Multienzyme Complexes / genetics
  • Multienzyme Complexes / metabolism
  • Mycobacterium smegmatis / chemistry
  • Mycobacterium smegmatis / enzymology*
  • Oxidation-Reduction
  • Protein Subunits / chemistry
  • Protein Subunits / metabolism
  • Structure-Activity Relationship
  • Succinate Dehydrogenase / chemistry*
  • Succinate Dehydrogenase / metabolism
  • Succinic Acid / metabolism
  • Vitamin K 2 / metabolism

Substances

  • Bacterial Proteins
  • Multienzyme Complexes
  • Protein Subunits
  • Vitamin K 2
  • Succinic Acid
  • Succinate Dehydrogenase