Apr 4, 2020

Hydrogen-deuterium exchange mass spectrometry captures distinct dynamics upon substrate and inhibitor binding to a transporter

BioRxiv : the Preprint Server for Biology
R. JiaArgyris Politis

Abstract

Proton-coupled transporters use transmembrane proton gradients to power active transport of nutrients inside the cell. High-resolution structures often fail to capture the coupling between proton and ligand binding, and conformational changes associated with transport. We combine HDX-MS with mutagenesis and MD simulations to dissect the molecular mechanism of the prototypical transporter XylE. We show that protonation of a conserved aspartate triggers conformational transition from outward- facing to inward-facing state. This transition only occurs in the presence of substrate xylose, while the inhibitor glucose locks the transporter in the outward-facing state. MD simulations corroborate the experiments by showing that only the combination of protonation and xylose binding, and not glucose, sets up the transporter for conformational switch. Overall, we demonstrate the unique ability of HDX-MS to distinguish between the conformational dynamics of inhibitor and substrate binding, and show that a specific allosteric coupling between substrate binding and protonation is a key step to initiate transport.

  • References
  • Citations

References

  • We're still populating references for this paper, please check back later.
  • References
  • Citations

Citations

  • This paper may not have been cited yet.

Mentioned in this Paper

Study
Sporulation
Extracellular
Membrane
Cell Motility
Pathogenic Organism
Complex (molecular entity)
Motility
Basal Bodies
Mass Spectrometry

Related Feeds

Biofilms

Biofilms are adherent bacterial communities embedded in a polymer matrix and can cause persistent human infections that are highly resistant to antibiotics. Discover the latest research on Biofilms here.

Biofilm & Infectious Disease

Biofilm formation is a key virulence factor for a wide range of microorganisms that cause chronic infections.Here is the latest research on biofilm and infectious diseases.

BioRxiv & MedRxiv Preprints

BioRxiv and MedRxiv are the preprint servers for biology and health sciences respectively, operated by Cold Spring Harbor Laboratory. Here are the latest preprint articles (which are not peer-reviewed) from BioRxiv and MedRxiv.