Referenced in: none

Automatically associated channels: Slo1

Title: Resting state of the human proton channel dimer in a lipid bilayer.

Authors: Qufei Li, Rong Shen, Jeremy S Treger, Sherry S Wanderling, Wieslawa Milewski, Klaudia Siwowska, Francisco Bezanilla, Eduardo Perozo

Journal, date & volume: Proc. Natl. Acad. Sci. U.S.A., 2015 Nov 3 , 112, E5926-35

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/26443860

Abstract
The voltage-gated proton channel Hv1 plays a critical role in the fast proton translocation that underlies a wide range of physiological functions, including the phagocytic respiratory burst, sperm motility, apoptosis, and metastatic cancer. Both voltage activation and proton conduction are carried out by a voltage-sensing domain (VSD) with strong similarity to canonical VSDs in voltage-dependent cation channels and enzymes. We set out to determine the structural properties of membrane-reconstituted human proton channel (hHv1) in its resting conformation using electron paramagnetic resonance spectroscopy together with biochemical and computational methods. We evaluated existing structural templates and generated a spectroscopically constrained model of the hHv1 dimer based on the Ci-VSD structure at resting state. Mapped accessibility data revealed deep water penetration through hHv1, suggesting a highly focused electric field, comprising two turns of helix along the fourth transmembrane segment. This region likely contains the H(+) selectivity filter and the conduction pore. Our 3D model offers plausible explanations for existing electrophysiological and biochemical data, offering an explicit mechanism for voltage activation based on a one-click sliding helix conformational rearrangement.