ATP binding drives substrate capture in an ECF transporter by a release-and-catch mechanism

Nat Struct Mol Biol. 2015 Jul;22(7):565-71. doi: 10.1038/nsmb.3040. Epub 2015 Jun 8.

Abstract

ECF transporters are a family of active transporters for vitamins. They are composed of four subunits: a membrane-embedded substrate-binding subunit (EcfS), a transmembrane coupling subunit (EcfT) and two ATP-binding-cassette ATPases (EcfA and EcfA'). We have investigated the mechanism of the ECF transporter for riboflavin from the pathogen Listeria monocytogenes, LmECF-RibU. Using structural and biochemical approaches, we found that ATP binding to the EcfAA' ATPases drives a conformational change that dissociates the S subunit from the EcfAA'T ECF module. Upon release from the ECF module, the RibU S subunit then binds the riboflavin transport substrate. We also find that S subunits for distinct substrates compete for the ATP-bound state of the ECF module. Our results explain how ECF transporters capture the transport substrate and reproduce the in vivo observations on S-subunit competition for which the family was named.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism*
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / metabolism*
  • Crystallography, X-Ray
  • Humans
  • Listeria monocytogenes / chemistry
  • Listeria monocytogenes / metabolism*
  • Listeriosis / microbiology
  • Membrane Transport Proteins / chemistry
  • Membrane Transport Proteins / metabolism*
  • Models, Molecular
  • Protein Conformation
  • Protein Multimerization
  • Protein Subunits / chemistry
  • Protein Subunits / metabolism
  • Riboflavin / metabolism*

Substances

  • Bacterial Proteins
  • Membrane Transport Proteins
  • Protein Subunits
  • Adenosine Triphosphate
  • Riboflavin

Associated data

  • PDB/4ZIR