Gating interaction maps reveal a noncanonical electromechanical coupling mode in the Shaker K+ channel.

Fernández-Mariño AI, Harpole TJ, Oelstrom K, Delemotte L, Chanda B

Nat. Struct. Mol. Biol. 25 (4) 320-326 [2018-04-00; online 2018-03-26]

Membrane potential regulates the activity of voltage-dependent ion channels via specialized voltage-sensing modules, but the mechanisms involved in coupling voltage-sensor movement to pore opening remain unclear owing to a lack of resting state structures and robust methods to identify allosteric pathways. Here, using a newly developed interaction-energy analysis, we probe the interfaces of the voltage-sensing and pore modules in the Drosophila Shaker K+ channel. Our measurements reveal unexpectedly strong equilibrium gating interactions between contacts at the S4 and S5 helices in addition to those between S6 and the S4-S5 linker. Network analysis of MD trajectories shows that the voltage-sensor and pore motions are linked by two distinct pathways: a canonical pathway through the S4-S5 linker and a hitherto unknown pathway akin to rack-and-pinion coupling involving the S4 and S5 helices. Our findings highlight the central role of the S5 helix in electromechanical transduction in the voltage-gated ion channel (VGIC) superfamily.

Affiliated researcher

Lucie Delemotte

SciLifeLab Fellow

PubMed 29581567

DOI 10.1038/s41594-018-0047-3

Crossref 10.1038/s41594-018-0047-3

pii: 10.1038/s41594-018-0047-3
pmc: PMC6170002
mid: NIHMS940398

Publications 9.5.0