Work

Sodium and proton coupling in the conformational cycle of a MATE antiporter from Vibrio cholerae

Year: 2018

Type: article

Abstract: Significance Transporters from the multidrug and toxic compound extrusion (MATE) superfamily protect the cell from cytotoxic molecules through an efflux mechanism that is dependent on ion electrochemical gradients. This study examined the role of specific residues in supporting conformational changes associated with ion and drug binding in NorM, an archetype of MATE transporters. The results show that a network of conserved residues in the N-terminal domain is critical for Na + - and H + -driven conformational changes, whereas residues in the C-terminal domain mediate drug binding. Informed by a correlation of conformational dynamics with transport activity, we propose a model that describes how conserved residues mediate ion-coupled structural changes underlying drug efflux.

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.1802417115

Authors: Derek P. Claxton, Kevin L. Jagessar, P. Ryan Steed, Richard A. Stein, Hassane S. Mchaourab

Institution: Vanderbilt University

Language: English

Topic: Drug Transport and Resistance Mechanisms

Subfield: Oncology

Field: Medicine

Domain: Health Sciences

Open Access status: green

Funder: National Institute of General Medical Sciences

Award: Structural Dynamics of Multi-drug Transporters