1. Howard Hughes Medical Institute, Laboratory of Molecular Neurobiology and Biophysics and Laboratory of Mass Spectrometry and Gaseous Ion Chemistry, Rockefeller University, 1230 York Avenue, New York, New York 10021, USA

Correspondence to: Roderick MacKinnon Correspondence and requests for materials should be addressed to R.M. (e-mail: Email: mackinn@rockvax.rockefeller.edu). Coordinates have been deposited with the Protein Data Bank under accession code 1LNQ.

Abstract

Living cells regulate the activity of their ion channels through a process known as gating. To open the pore, protein conformational changes must occur within a channel's membrane-spanning ion pathway. KcsA and MthK, closed and opened K⁺ channels, respectively, reveal how such gating transitions occur. Pore-lining 'inner' helices contain a 'gating hinge' that bends by approximately 30°. In a straight conformation four inner helices form a bundle, closing the pore near its intracellular surface. In a bent configuration the inner helices splay open creating a wide (12 Å) entryway. Amino-acid sequence conservation suggests a common structural basis for gating in a wide range of K⁺ channels, both ligand- and voltage-gated. The open conformation favours high conduction by compressing the membrane field to the selectivity filter, and also permits large organic cations and inactivation peptides to enter the pore from the intracellular solution.

1. Howard Hughes Medical Institute, Laboratory of Molecular Neurobiology and Biophysics and Laboratory of Mass Spectrometry and Gaseous Ion Chemistry, Rockefeller University, 1230 York Avenue, New York, New York 10021, USA

Correspondence to: Roderick MacKinnon Correspondence and requests for materials should be addressed to R.M. (e-mail: Email: mackinn@rockvax.rockefeller.edu). Coordinates have been deposited with the Protein Data Bank under accession code 1LNQ.