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

Ruyu Jia; Chloe Martens; Mrinal Shekhar; Shashank Pant; Grant A. Pellowe; Andy M. Lau; Heather E. Findlay; Nicola J. Harris; Emad Tajkhorshid; Paula J. Booth; Argyris Politis

doi:10.1038/s41467-020-20032-3

Nature Communications (Dec 2020)

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

Ruyu Jia,
Chloe Martens,
Mrinal Shekhar,
Shashank Pant,
Grant A. Pellowe,
Andy M. Lau,
Heather E. Findlay,
Nicola J. Harris,
Emad Tajkhorshid,
Paula J. Booth,
Argyris Politis

Affiliations

Ruyu Jia: Department of Chemistry, King’s College London
Chloe Martens: Department of Chemistry, King’s College London
Mrinal Shekhar: Center for Biophysics and Quantitative Biology, Department of Biochemistry, NIH Center for Macromolecular Modeling and Bioinformatics, Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign
Shashank Pant: Center for Biophysics and Quantitative Biology, Department of Biochemistry, NIH Center for Macromolecular Modeling and Bioinformatics, Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign
Grant A. Pellowe: Department of Chemistry, King’s College London
Andy M. Lau: Department of Chemistry, King’s College London
Heather E. Findlay: Department of Chemistry, King’s College London
Nicola J. Harris: Department of Chemistry, King’s College London
Emad Tajkhorshid: Center for Biophysics and Quantitative Biology, Department of Biochemistry, NIH Center for Macromolecular Modeling and Bioinformatics, Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign
Paula J. Booth: Department of Chemistry, King’s College London
Argyris Politis: Department of Chemistry, King’s College London

DOI: https://doi.org/10.1038/s41467-020-20032-3
Journal volume & issue: Vol. 11, no. 1
pp. 1 – 10

Abstract

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XylE is a bacterial xylose transporter and homologue of human glucose transporters GLUTs 1-4. HDX-MS, mutagenesis and MD simulations suggest that protonation of a conserved aspartate triggers conformational transition from outward- to inward facing state only in the presence of substrate xylose. In contrast, inhibitor glucose locks the transporter in the outward facing state.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

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