Biophysical Society Conference | Tahoe 2022

Molecular Biophysics of Membranes

Wednesday Speaker Abstracts

KINETIC SELECTION OF COMPETING ION EXCHANGE PATHWAYS: WHEN DOES THE ELECTRICAL VERSUS CHEMICAL GRADIENT MATTER? Jessica MJ Swanson 1 ; 1 The University of Utah, Department of Chemistry, Salt Lake City, UT, USA It is increasingly apparent that membrane transport mechanisms can involve kinetic selection between competing pathways, each with a different sequence of transitions between intermediates during the transport process. Moreover, the dominance of these pathways can shift under different reaction conditions. In this talk the mechanistic reaction network for coupled Cl– /H+ exchange in ClC antiporters will be described. Using a multiscale kinetic modeling approach that integrates experimental and simulation data the dominance of different pathways will be shown to shift as a function of pH. This highlights the importance of the lower H+ binding site, which has had a questionable role in the transport cycle to date, in maintaining the ion exchange ratio over a range of pH values. The flux will also be shown to shift in response to transmembrane electrochemical potentials. Interestingly, these effects will be shown to be different for an electrical gradient vs chemical gradient of the same magnitude, pointing to a more nuanced influence of electrochemical potentials than commonly assumed by the Nernst relationship.

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