Campus Units

Chemistry

Document Type

Article

Publication Version

Accepted Manuscript

Publication Date

1-2011

Journal or Book Title

Biochimica et Biophysica Acta (BBA) - Biomembranes

Volume

1808

Issue

1

First Page

415

Last Page

423

DOI

10.1016/j.bbamem.2010.09.014

Abstract

Membrane proteins change their conformations to respond to environmental cues, thus conformational plasticity is important for function. The influenza A M2 protein forms an acid-activated proton channel important for the virus lifecycle. Here we have used solid-state NMR spectroscopy to examine the conformational plasticity of membrane-bound transmembrane domain of M2 (M2TM). 13C and 15N chemical shifts indicate coupled conformational changes of several pore-facing residues due to changes in bilayer thickness, drug binding, and pH. The structural changes are attributed to the formation of a well-defined helical kink at G34 in the drug-bound state and in thick lipid bilayers, nonideal backbone conformation of the secondary-gate residue V27 in the presence of drug, and nonideal conformation of the proton-sensing residue H37 at high pH. The chemical shifts constrained the (ϕ, ψ) torsion angles for three “basis” states, the equilibrium among which explains the multiple resonances per site in the NMR spectra under different combinations of bilayer thickness, drug binding, and pH conditions. Thus, conformational plasticity is important for the proton conduction and inhibition of M2TM. The study illustrates the utility of NMR chemical shifts for probing the structural plasticity and folding of membrane proteins.

Comments

This is a manuscript of an article published as Hu, Fanghao, Wenbin Luo, Sarah D. Cady, and Mei Hong. "Conformational plasticity of the influenza A M2 transmembrane helix in lipid bilayers under varying pH, drug binding, and membrane thickness." Biochimica et Biophysica Acta (BBA)-Biomembranes 1808, no. 1 (2011): 415-423. DOI: 10.1016/j.bbamem.2010.09.014. Posted with permission.

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

Copyright Owner

Elsevier B.V.

Language

en

File Format

application/pdf

Published Version

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