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Cited by 90Advanced NMR Techniques and ApplicationsElectron Spin Resonance StudiesLipid Membrane Structure and Behavior

Conformational Changes of an Ion Channel Detected Through Water−Protein Interactions Using Solid-State NMR Spectroscopy

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Luo, Wenbin, Hong, Mei·2010·Journal of the American Chemical Society
DOI 10.1021/ja9096219PMC PMC2829254
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Abstract

The influenza A virus M2 protein is a pH-gated and amantadine-inhibited proton channel important for the virus life cycle. Proton conduction by M2 is known to involve water; however direct experimental evidence of M2-water interaction is scarce. Using (1)H spin diffusion solid-state NMR, we have now determined the water accessibility of the M2 transmembrane domain (M2-TM) in virus-envelope-mimetic lipid membranes and its changes with environment. Site-specific water-protein magnetization transfer indicates that, in the absence of amantadine, the initial spin diffusion rate mainly depends on the radial position of the residues from the pore: pore-lining residues along the helix have similarly high water accessibilities compared to lipid-facing residues. Upon drug binding, the spin diffusion rates become much slower for Gly(34) in the middle of the helix than for the N-terminal residues, indicating that amantadine is bound to the pore lumen between Gly(34) and Val(27). Water-protein spin diffusion buildup curves indicate that spin diffusion is the fastest in the low-pH open state, slower in the high-pH closed state, and the slowest in the high-pH amantadine-bound state. Simulations of the buildup curves using a 3D lattice model yielded quantitative values of the water-accessible surface area and its changes by pH and drug binding. These data provide direct experimental evidence of the pH-induced change of the pore size and the drug-induced dehydration of the pore. This study demonstrates the capability of (1)H spin diffusion NMR for elucidating water interactions with ion channels, water pores, and proton pumps and for probing membrane protein conformational changes that involve significant changes of water-accessible surface areas.

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  • The relative intensity ratio between the water-edited spectrum and the control spectrum reflects the extent of hydration of cell wall samples.

    “The relative intensity ratio between the water-edited spectrum and the control spectrum was quantified for all cell wall samples to reflect the extent of hydration.”

    From Distinct echinocandin responses of Candida albicans and Candida auris cell walls revealed by solid-state NMR (2025) · cites this paper as [122]

    In Results and Discussion, under “Differential water accessibilities of M2-TM” (page unavailable), the paper uses relative NMR water-signal intensities to assess water accessibility in a membrane protein. It does not study cell wall samples or establish that the ratio of a water-edited spectrum to a control spectrum measures their extent of hydration. (LLM, conf=0.82)

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Authors
Luo, W., & Hong, M.
Affiliations
Iowa State University (US)
Corresponding author
Hong, Mei
ORCID
Venue
Journal of the American Chemical Society
Publisher
American Chemical Society (ACS)
Published
2010-01-29
Volume
132
Issue
7
Pages
2378-2384
ISSN
  • 0002-7863 (ISSN-L)
  • 1520-5126
DOI
10.1021/ja9096219
PMC
PMC2829254
OpenAlex
W1974390195
Cited by
90
References
0
Citations by year
2026: 4 · 2025: 5 · 2024: 3 · 2023: 5 · 2022: 4 · 2021: 5 · 2020: 3 · 2019: 3 · 2018: 4 · 2017: 8 · 2016: 4 · 2015: 2 · 2014: 8 · 2013: 7 · 2012: 10
FWCI
4.70
Type
journal article
Language
en
Open access
Locations
  • Journal of the American Chemical Society (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute of General Medical Sciences (R01GM088204)
Topics
  • Physical Sciences › Chemistry › Spectroscopy › Advanced NMR Techniques and Applications
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Electron Spin Resonance Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
Keywords
influenza A virus M2 protein, proton channel, amantadine, protein-water interactions, spin diffusion, water access, transmembrane domain, pH gating, pore size, conformational change, lipid membranes, 3D lattice model
MeSH terms
Viroporin Proteins, Amantadine, Amino Acid Sequence, Computer Simulation, Diffusion, Hydrogen-Ion Concentration, Ion Channels, Molecular Sequence Data, Protein Conformation, Surface Properties, Viral Matrix Proteins, Water, Nuclear Magnetic Resonance, Biomolecular

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