A molecular mechanism for proton-dependent gating in KcsA |
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Authors: | Luis G. Cuello Vishwanath Jogini Eduardo Perozo |
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Affiliation: | a Department of Biochemistry and Molecular Biology, The University of Chicago, 929 E 57th Street, Chicago, IL 60637, USA b Institute for Biophysical Dynamics, The University of Chicago, 929 E 57th Street, Chicago, IL 60637, USA |
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Abstract: | Activation gating in KcsA is elicited by changes in intracellular proton concentration. Thompson et al. [1] identified a charge cluster around the inner gate that plays a key role in defining proton activation in KcsA. Here, through functional and spectroscopic approaches, we confirmed the role of this charge cluster and now provide a mechanism of pH-dependent gating. Channel opening is driven by a set of electrostatic interactions that include R117, E120 and E118 at the bottom of TM2 and H25 at the end of TM1. We propose that electrostatic compensation in this charge cluster stabilizes the closed conformation at neutral pH and that its disruption at low pH facilitates the transition to the open conformation by means of helix-helix repulsion. |
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Keywords: | Ion channel KcsA Activation gating pH-dependence Electrostatic interaction |
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