Journal article
Elucidating Relayed Proton Transfer through a His-Trp-His Triad of a Transmembrane Proton Channel by Solid-State NMR
Journal of molecular biology, Vol.431(14), pp.2554-2566
06/28/2019
DOI: 10.1016/j.jmb.2019.05.009
PMCID: PMC6589385
PMID: 31082440
Abstract
Proton transfer through membrane-bound ion channels is mediated by both water and polar residues of proteins, but the detailed molecular mechanism is challenging to determine. The tetrameric influenza A and B virus M2 proteins form canonical proton channels that use an HxxxW motif for proton selectivity and gating. The BM2 channel also contains a second histidine (His), H27, equidistant from the gating tryptophan, which leads to a symmetric H(19)xxxW(23)xxxH(27) motif. The proton-dissociation constants (pKa's) of H19 in BM2 were found to be much lower than the pKa's of H37 in AM2. To determine if the lower pKa's result from H27-facilitated proton dissociation of H19, we have now investigated a H27A mutant of BM2 using solid-state NMR. N-15 NMR spectra indicate that removal of the second histidine converted the protonation and tautomeric equilibria of H19 to be similar to the H37 behavior in AM2, indicating that the peripheral H27 is indeed the origin of the low pKa's of H19 in wild-type BM2. Measured interhelical distances between W23 sidechains indicate that the pore constriction at W23 increases with the H19 tetrad charge but is independent of the H27A mutation. These results indicate that H27 both accelerates proton dissociation from H19 to increase the inward proton conductance and causes the small reverse conductance of BM2. The proton relay between H19 and H27 is likely mediated by the intervening gating tryptophan through cation-pi interactions. This relayed proton transfer may exist in other ion channels and has implications for the design of imidazole-based synthetic proton channels. (C) 2019 Elsevier Ltd. All rights reserved.
Details
- Title: Subtitle
- Elucidating Relayed Proton Transfer through a His-Trp-His Triad of a Transmembrane Proton Channel by Solid-State NMR
- Creators
- Byungsu Kwon - MIT, Dept Chem, 170 Albany St, Cambridge, MA 02139 USAMatthias Roos - Massachusetts Institute of TechnologyVenkata S. Mandala - Massachusetts Institute of TechnologyAlexander A. Shcherbakov - Massachusetts Institute of TechnologyMei Hong - Massachusetts Institute of Technology
- Resource Type
- Journal article
- Publication Details
- Journal of molecular biology, Vol.431(14), pp.2554-2566
- DOI
- 10.1016/j.jmb.2019.05.009
- PMID
- 31082440
- PMCID
- PMC6589385
- NLM abbreviation
- J Mol Biol
- ISSN
- 0022-2836
- eISSN
- 1089-8638
- Publisher
- Elsevier
- Number of pages
- 13
- Grant note
- R01GM088204 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) GM088204 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA LPDS-2017-14 / German National Academy of Sciences Leopoldina postdoctoral fellowship
- Language
- English
- Date published
- 06/28/2019
- Academic Unit
- Biochemistry and Molecular Biology
- Record Identifier
- 9985112880502771
Metrics
1 Record Views