Trapped Pore Waters in the Open Proton Channel HV1. Issue 16 (22nd January 2023)

• Record Type: Journal Article
• Authors: Boytsov, Danila; Brescia, Stefania; Chaves, Gustavo; Koefler, Sabina; Hannesschlaeger, Christof; Siligan, Christine; Goessweiner‐Mohr, Nikolaus; Musset, Boris; Pohl, Peter
• Is Part Of: Small. Volume 19:Issue 16(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2023-01-22
• Subjects: electrophysiology -- fluorimetry -- membrane transport -- proteoliposomes -- voltage gated channels; Nanotechnology -- Periodicals; Nanoparticles -- Periodicals; Microtechnology -- Periodicals; 620.5
• DOI: 10.1002/smll.202205968
• Languages: English
• ISSNs: 1613-6810

Abstract

Abstract: The voltage‐gated proton channel, HV 1, is crucial for innate immune responses. According to alternative hypotheses, protons either hop on top of an uninterrupted water wire or bypass titratable amino acids, interrupting the water wire halfway across the membrane. To distinguish between both hypotheses, the water mobility for the putative case of an uninterrupted wire is estimated. The predicted single‐channel water permeability 2.3 × 10 −12 cm 3 s −1 reflects the permeability‐governing number of hydrogen bonds between water molecules in single‐file configuration and pore residues. However, the measured unitary water permeability does not confirm the predicted value. Osmotic deflation of reconstituted lipid vesicles reveals negligible water permeability of the HV 1 wild‐type channel and the D174A mutant open at 0 mV. The conductance of 1400 H + s −1 per wild‐type channel agrees with the calculated diffusion limit for a ≈2 Å capture radius for protons. Removal of a charged amino acid (D174) at the pore mouth decreases H + conductance by reducing the capture radius. At least one intervening amino acid contributes to H + conductance while interrupting the water wire across the membrane. Abstract : Proton hopping through the human voltage‐gated proton channel HV 1 involves pore‐lining amino acid residues rather than an unbroken water chain. The high unitary channel conductance for protons contrasts with the incapability to facilitate water transport. An HV 1 mutant enables the observation of the open state when no membrane potential is applied.