Proton currents constrain structural models of voltage sensor activation.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 27572256.
- Also identified by DOI 10.7554/eLife.18017 and PMC identifier 5065317.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
The Hv1 proton channel is evidently unique among voltage sensor domain proteins in mediating an intrinsic 'aqueous' H<sup>+</sup> conductance (G<sub>AQ</sub>). Mutation of a highly conserved 'gating charge' residue in the S4 helix (R1H) confers a resting-state H<sup>+</sup> 'shuttle' conductance (G<sub>SH</sub>) in VGCs and Ci VSP, and we now report that R1H is sufficient to reconstitute G<sub>SH</sub> in Hv1 without abrogating G<sub>AQ</sub>. Second-site mutations in S3 (D185A/H) and S4 (N4R) experimentally separate G<sub>SH</sub> and G<sub>AQ</sub> gating, which report thermodynamically distinct initial and final steps, respectively, in the Hv1 activation pathway. The effects of Hv1 mutations on G<sub>SH</sub> and G<sub>AQ</sub> are used to constrain the positions of key side chains in resting- and activated-state VS model structures, providing new insights into the structural basis of VS activation and H<sup>+</sup> transfer mechanisms in Hv1.
Medical subject headings
- Ion Channels
- Mutant Proteins
- Protons