Visualizing the nonlinear changes of a drug-proton antiporter from inward-open to occluded state

Biochem Biophys Res Commun. 2021 Jan 1:534:272-278. doi: 10.1016/j.bbrc.2020.11.096. Epub 2020 Dec 3.

Abstract

Drug-proton antiporters (DHA) play an important role in multi-drug resistance, utilizing the proton-motive force to drive the expulsion of toxic molecules, including antibiotics and drugs. DHA transporters belong to the major facilitator superfamily (MFS), members of which deliver substrates by utilizing the alternating access model of transport. However, the transport process is still elusive. Here, we report the structures of SotB, a member of DHA1 family (TCDB: 2.A.1.2) from Escherichia coli. Four crystal structures of SotB were captured in different conformations, including substrate-bound occluded, inward-facing, and inward-open states. Comparisons between the four structures reveal nonlinear rigid-body movements of alternating access during the state transition from inward-open to occluded conformation. This work not only reveals the conformational dynamics of SotB but also deepens our understanding of the alternating access mechanism of MFS transporters.

Keywords: Crystal structure; Drug-proton antiporter; Multiple conformations; Nonlinear change; SotB.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiporters / chemistry*
  • Antiporters / genetics
  • Antiporters / metabolism*
  • Biological Transport, Active
  • Crystallography, X-Ray
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Escherichia coli Proteins / chemistry*
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism*
  • Models, Molecular
  • Molecular Dynamics Simulation
  • Mutagenesis, Site-Directed
  • Protein Conformation
  • Protein Domains
  • Proton-Motive Force
  • Protons
  • Static Electricity

Substances

  • Antiporters
  • Escherichia coli Proteins
  • Protons