Domain-swapped Chain Connectivity and Gated Membrane Access in a Fab-mediated Crystal of the Human TRAAK K+ Channel

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2013 Jan 24

PMID 23341632

Citations 69

Authors

Stephen G Brohawn

Ernest B Campbell

Roderick MacKinnon

Affiliations

Soon will be listed here.

Abstract

TRAAK (TWIK-related arachidonic acid-stimulated K(+) channel, K2P4.1) K(+) ion channels are expressed predominantly in the nervous system to control cellular resting membrane potential and are regulated by mechanical and chemical properties of the lipid membrane. TRAAK channels are twofold symmetric, which precludes a direct extension of gating mechanisms that close canonical fourfold symmetric K(+) channels. We present the crystal structure of human TRAAK in complex with antibody antigen-binding fragments (Fabs) at 2.75-Å resolution. In contrast to a previous structure, this structure reveals a domain-swapped chain connectivity enabled by the helical cap that exchanges two opposing outer helices 180° around the channel. An unrelated conformational change of an inner helix seals a side opening to the membrane bilayer and is associated with structural changes around the K(+)-selectivity filter that may have implications for mechanosensitivity and gating of TRAAK channels.

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