Interplay between membrane curvature and protein conformational equilibrium investigated by solid-state NMR
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nihms951727.pdf
Description
Accepted version
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1.46 MB
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Checksum (MD5)
585111cbb9653b496197897a16b368f2
Author(s)
Liao, Shu Y.
Lee, Myungwoon
Hong, Mei
Date Issued
April 2019
Journal
Journal of structural biology
Publisher
Elsevier BV
Citation
Liao, Shu Y., Myungwoon Lee, and Mei Hong, "Interplay between membrane curvature and protein conformational equilibrium investigated by solid-state NMR." Journal of structural biology 206, 1 (April 2019): p. 20-28 doi 10.1016/J.JSB.2018.02.007 ©2019 Author(s)
Version
Author's final manuscript
Abstract
Many membrane proteins sense and induce membrane curvature for function, but structural information about how proteins modulate their structures to cause membrane curvature is sparse. We review our recent solid-state NMR studies of two virus membrane proteins whose conformational equilibrium is tightly coupled to membrane curvature. The influenza M2 proton channel has a drug-binding site in the transmembrane (TM) pore. Previous chemical shift data indicated that this pore-binding site is lost in an M2 construct that contains the TM domain and a curvature-inducing amphipathic helix. We have now obtained chemical shift perturbation, protein-drug proximity, and drug orientation data that indicate that the pore-binding site is restored when the full cytoplasmic domain is present. This finding indicates that the curvature-inducing amphipathic helix distorts the TM structure to interfere with drug binding, while the cytoplasmic tail attenuates this effect. In the second example, we review our studies of a parainfluenza virus fusion protein that merges the cell membrane and the virus envelope during virus entry. Chemical shifts of two hydrophobic domains of the protein indicate that both domains have membrane-dependent backbone conformations, with the β-strand structure dominating in negative-curvature phosphatidylethanolamine (PE) membranes. 31 P NMR spectra and 1 H- 31 P correlation spectra indicate that the β-strand-rich conformation induces saddle-splay curvature to PE membranes and dehydrates them, thus stabilizing the hemifusion state. These results highlight the indispensable role of solid-state NMR to simultaneously determine membrane protein structures and characterize the membrane curvature in which these protein structures exist. ©2019
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
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Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
10.1016/J.JSB.2018.02.007
