Exploring the Ligand Binding and Conformational Dynamics of the Substrate-Binding Domain 1 of the ABC Transporter GlnPQ

J Phys Chem B. 2024 Aug 15;128(32):7822-7832. doi: 10.1021/acs.jpcb.4c02662. Epub 2024 Aug 1.

Abstract

The adenosine triphosphate (ATP)-binding cassette (ABC) importer GlnPQ from Lactococcus lactis has two sequential covalently linked substrate-binding domains (SBDs), which capture the substrates and deliver them to the translocon. The two SBDs differ in their ligand specificities, binding affinities and the distance to the transmembrane domain; interestingly, both SBDs can bind their ligands simultaneously without affecting each other. In this work, we studied the binding of ligands to both SBDs using X-ray crystallography and molecular dynamics simulations. We report three high-resolution structures of SBD1, namely, the wild-type SBD1 with bound asparagine or arginine, and E184D SBD1 with glutamine bound. Molecular dynamics (MD) simulations provide a detailed insight into the dynamics associated with open-closed transitions of the SBDs.

MeSH terms

  • ATP-Binding Cassette Transporters* / chemistry
  • ATP-Binding Cassette Transporters* / metabolism
  • Bacterial Proteins* / chemistry
  • Bacterial Proteins* / metabolism
  • Binding Sites
  • Carrier Proteins
  • Crystallography, X-Ray
  • Lactococcus lactis* / chemistry
  • Lactococcus lactis* / metabolism
  • Ligands
  • Molecular Dynamics Simulation*
  • Protein Binding
  • Protein Conformation
  • Protein Domains

Substances

  • Ligands
  • ATP-Binding Cassette Transporters
  • Bacterial Proteins
  • glutamine transport proteins
  • Carrier Proteins