Atomic structures of closed and open influenza B M2 proton channel reveal the conduction mechanism

Venkata S. Mandala; Alexander R. Loftis; Alexander A. Shcherbakov; Bradley L. Pentelute; Mei Hong

doi:10.1038/s41594-019-0371-2

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Atomic structures of closed and open influenza B M2 proton channel reveal the conduction mechanism

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Atomic structures of closed and open influenza B M2 proton channel reveal the conduction mechanism

Venkata S. Mandala, Alexander R. Loftis, Alexander A. Shcherbakov, Bradley L. Pentelute and Mei Hong

Nature structural & molecular biology, Vol.27(2), pp.160-167

02/01/2020

DOI: 10.1038/s41594-019-0371-2

PMCID: PMC7641042

PMID: 32015551

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https://www.ncbi.nlm.nih.gov/pmc/articles/7641042View

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Abstract

The influenza B M2 (BM2) proton channel is activated by acidic pH to mediate virus uncoating. Unlike influenza A M2 (AM2), which conducts protons with strong inward rectification, BM2 conducts protons both inward and outward. Here we report 1.4- and 1.5-Å solid-state NMR structures of the transmembrane domain of the closed and open BM2 channels in a phospholipid environment. Upon activation, the transmembrane helices increase the tilt angle by 6° and the average pore diameter enlarges by 2.1 Å. BM2 thus undergoes a scissor motion for activation, which differs from the alternating-access motion of AM2. These results indicate that asymmetric proton conduction requires a backbone hinge motion, whereas bidirectional conduction is achieved by a symmetric scissor motion. The proton-selective histidine and gating tryptophan in the open BM2 reorient on the microsecond timescale, similar to AM2, indicating that side chain dynamics are the essential driver of proton shuttling. Solid-state NMR structures of the influenza B M2 (BM2) proton channel transmembrane domain in a phospholipid environment reveal open and closed conformations and indicate that side chain dynamics are essential for proton shuttling by BM2.

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Article

Biochemistry

Biological Microscopy

Biomedical and Life Sciences

General

Life Sciences

Membrane Biology

Protein Structure

Details

Title: Subtitle: Atomic structures of closed and open influenza B M2 proton channel reveal the conduction mechanism
Creators: Venkata S. Mandala - Massachusetts Institute of Technology
Alexander R. Loftis - Massachusetts Institute of Technology
Alexander A. Shcherbakov - Massachusetts Institute of Technology
Bradley L. Pentelute - Massachusetts Institute of Technology
Mei Hong - Massachusetts Institute of Technology
Resource Type: Journal article
Publication Details: Nature structural & molecular biology, Vol.27(2), pp.160-167
DOI: 10.1038/s41594-019-0371-2
PMID: 32015551
PMCID: PMC7641042
NLM abbreviation: Nat Struct Mol Biol
ISSN: 1545-9993
eISSN: 1545-9985
Publisher: Nature Publishing Group US
Number of pages: 8
Language: English
Date published: 02/01/2020
Academic Unit: Biochemistry and Molecular Biology
Record Identifier: 9985113008302771

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