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

Ion channels exhibit two essential biophysical properties; that is, selective ion conduction, and the ability to gate-open in response to an appropriate stimulus. Two general categories of ion channel gating are defined by the initiating stimulus: ligand binding (neurotransmitter- or second-messenger-gated channels) or membrane voltage (voltage-gated channels). Here we present the structural basis of ligand gating in a K⁺ channel that opens in response to intracellular Ca²⁺. We have cloned, expressed, analysed electrical properties, and determined the crystal structure of a K⁺ channel (MthK) from Methanobacterium thermoautotrophicum in the Ca²⁺-bound, opened state. Eight RCK domains (regulators of K⁺ conductance) form a gating ring at the intracellular membrane surface. The gating ring uses the free energy of Ca²⁺ binding in a simple manner to perform mechanical work to open the pore.

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.