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Domain-swapped chain connectivity and gated membrane access in a Fab-mediated crystal of the human TRAAK K+ channel.

Brohawn SG, Campbell EB, MacKinnon R
Proc Natl Acad Sci U S A 110 2129-34 (2013)
Cited: 83 times
EuropePMC logo PMID: 23341632

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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  1. Structure of potassium channels. Kuang Q, Purhonen P, Hebert H. Cell Mol Life Sci 72 3677-3693 (2015)

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  10. Two-pore domain potassium channels: potential therapeutic targets for the treatment of pain. Mathie A, Veale EL. Pflugers Arch 467 931-943 (2015)
  11. Bacterial voltage-gated sodium channels (BacNa(V)s) from the soil, sea, and salt lakes enlighten molecular mechanisms of electrical signaling and pharmacology in the brain and heart. Payandeh J, Minor DL. J Mol Biol 427 3-30 (2015)
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  17. Structural Insights into the Mechanisms and Pharmacology of K2P Potassium Channels. Natale AM, Deal PE, Minor DL. J Mol Biol 433 166995 (2021)
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  19. Stretch-activated potassium currents in the heart: Focus on TREK-1 and arrhythmias. Decher N, Kiper AK, Rinné S. Prog Biophys Mol Biol 130 223-232 (2017)
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  23. The role of protein-protein interactions in the intracellular traffic of the potassium channels TASK-1 and TASK-3. Kilisch M, Lytovchenko O, Schwappach B, Renigunta V, Daut J. Pflugers Arch 467 1105-1120 (2015)
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Articles citing this publication (37)



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