A molecular mechanism for proton-dependent gating in KcsA

Cuello, Luis G.; Cortes, D. Marien; Jogini, Vishwanath; Sompornpisut, Amornrat; Perozo, Eduardo

doi:10.1016/j.febslet.2010.02.003

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Volume 584, Issue 6 , Pages 1126-1132, 19 March 2010

A molecular mechanism for proton-dependent gating in KcsA

Edited by Julian Schoeder

Luis G. Cuello
- Department of Biochemistry and Molecular Biology, The University of Chicago, 929 E 57th Street, Chicago, IL 60637, USA
D. Marien Cortes
- Department of Biochemistry and Molecular Biology, The University of Chicago, 929 E 57th Street, Chicago, IL 60637, USA
Vishwanath Jogini
- Department of Biochemistry and Molecular Biology, The University of Chicago, 929 E 57th Street, Chicago, IL 60637, USA
Amornrat Sompornpisut
- Department of Biochemistry and Molecular Biology, The University of Chicago, 929 E 57th Street, Chicago, IL 60637, USA
Eduardo Perozo
- Department of Biochemistry and Molecular Biology, The University of Chicago, 929 E 57th Street, Chicago, IL 60637, USA
- Institute for Biophysical Dynamics, The University of Chicago, 929 E 57th Street, Chicago, IL 60637, USA
- Corresponding author. Address: Department of Biochemistry and Molecular Biology, The University of Chicago, 929 E 57th Street, Chicago, IL 60637, USA. Fax: +1 773 834 4632.

Received 14 September 2009; received in revised form 1 February 2010; accepted 1 February 2010. published online 05 February 2010.

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.

Keywords: Ion channel, KcsA, Activation gating, pH-dependence, Electrostatic interaction