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Beyond Structural Biology to Functional Biology

Title: Beyond Structural Biology to Functional Biology: Solid-State NMR Experiments and Strategies for Understanding the M2 Proton Channel Conductance.
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Name(s): Qin, Huajun, author
Miao, Yimin, author
Cross, Timothy A, author
Fu, Riqiang, author
Type of Resource: text
Genre: Journal Article
Text
Date Issued: 2017-05-11
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: In terms of structural biology, solid-state NMR experiments and strategies have been well established for resonance assignments, leading to the determination of three-dimensional structures of insoluble membrane proteins in their native-like environment. It is also known that NMR has the unique capabilities to characterize structure-function relationships of membrane-bound biological systems beyond structural biology. Here, we report on solid-state NMR experiments and strategies for extracting functional activities on a sub-millisecond time scale. Specifically, we use the His37-labeled full length M2 (M2FL) protein of the Influenza A virus embedded in synthetic lipid bilayers as an example to characterize the proton conduction mechanism and kinetics. The integral membrane M2 protein assembles as a tetrameric bundle to form a proton-conducting channel that is activated by low pH and is essential for the viral lifecycle. Our results present convincing evidence for the formation of imidazolium-imidazole hydrogen bonds in the His37 tetrad at low pH and that these hydrogen bonds have a low barrier that facilitates the proton conduction mechanism in the M2FL protein. Moreover, it has been possible to measure hydronium ion exchange between water and the protons in the His37 NH bonds based on chemical exchange spectroscopy with minimized spin diffusion. The results identify an exchange rate constant of ∼4000 s for pH 5.8 at -10 °C.
Identifier: FSU_pmch_28425709 (IID), 10.1021/acs.jpcb.7b02468 (DOI), PMC5842430 (PMCID), 28425709 (RID), 28425709 (EID)
Grant Number: R01 AI023007, R01 AI119178
Publication Note: This NIH-funded author manuscript originally appeared in PubMed Central at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5842430.
Subject(s): Hydrogen-Ion Concentration
Influenza A virus/chemistry
Influenza A virus/metabolism
Lipid Bilayers/chemistry
Lipid Bilayers/metabolism
Nuclear Magnetic Resonance, Biomolecular
Viral Matrix Proteins/chemistry
Viral Matrix Proteins/isolation & purification
Viral Matrix Proteins/metabolism
Persistent Link to This Record: http://purl.flvc.org/fsu/fd/FSU_pmch_28425709
Host Institution: FSU
Is Part Of: The journal of physical chemistry. B.
1520-5207
Issue: iss. 18, vol. 121

Choose the citation style.
Qin, H., Miao, Y., Cross, T. A., & Fu, R. (2017). Beyond Structural Biology to Functional Biology: Solid-State NMR Experiments and Strategies for Understanding the M2 Proton Channel Conductance. The Journal Of Physical Chemistry. B. Retrieved from http://purl.flvc.org/fsu/fd/FSU_pmch_28425709