The Origin of Coupled Chloride and Proton Transport in a Cl-/H+ Antiporter

BioRxiv : the Preprint Server for Biology
Sangyun LeeGregory A Voth

Abstract

The ClC family of transmembrane proteins functions throughout nature to control the transport of Cl- ions across biological membranes. ClC-ec1 from Escherichia coli is an antiporter, coupling the transport of Cl- and H+ ions in opposite directions and driven by the concentration gradients of the ions. Despite keen interest in this protein, the molecular mechanism of the Cl-/H+ coupling has not been fully elucidated. Here, we have used multiscale simulation to help identify the essential mechanism of the Cl-/H+ coupling. We find that the highest barrier for proton transport (PT) from the intra- to extracellular solution is attributable to a chemical reaction—the deprotonation of glutamic acid 148 (E148). This barrier is significantly reduced by the binding of Cl- in the "central" site (Cl-cen), which displaces E148 and thereby facilitates its deprotonation. Conversely, in the absence of Cl-cen E148 favors the "down" conformation, which results in a much higher cumulative rotation and deprotonation barrier that effectively blocks PT to the extracellular solution. Thus, the rotation of E148 plays a critical role in defining the Cl-/H+ coupling. As a control, we have also simulated PT in the ClC-ec1 E148A mutant to further understa...Continue Reading

Related Concepts

Escherichia coli
Integral Membrane Proteins
Ions
Antiporter
Glutamic Acid
Site
Extracellular
Chloride Ion
Membrane
Gene Mutant

Related Feeds

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 Here are the latest preprint articles (which are not peer-reviewed) from BioRxiv and MedRxiv.

© 2021 Meta ULC. All rights reserved