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Journal article
Interplay between membrane curvature and protein conformational equilibrium investigated by solid-state NMR
Journal of structural biology, v 206(1)
01 Apr 2019
PMID: 29501472
Featured in Collection : UN Sustainable Development Goals @ Drexel
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.
P NMR spectra and
H-
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.
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Details
- Title
- Interplay between membrane curvature and protein conformational equilibrium investigated by solid-state NMR
- Creators
- Shu Y Liao - Massachusetts Institute of TechnologyMyungwoon Lee - Massachusetts Institute of TechnologyMei Hong - Massachusetts Institute of Technology
- Publication Details
- Journal of structural biology, v 206(1)
- Publisher
- Elsevier
- Grant note
- R01 GM088204 / NIGMS NIH HHS R01 GM066976 / NIGMS NIH HHS P41 EB002026 / NIBIB NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Chemistry
- Web of Science ID
- WOS:000465151300003
- Scopus ID
- 2-s2.0-85042879439
- Other Identifier
- 991021229880504721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Biochemistry & Molecular Biology
- Biophysics
- Cell Biology