Side Chain Structures of the Proton-Selective Histidine and Gating Tryptophan in Influenza BM2 Reveal Both Conservation and Variation of the Proton Conduction Mechanism
Name
nihms-2146595.pdf
Description
Accepted version
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2.44 MB
Format
Adobe PDF
Checksum (MD5)
928c03dbaaab28bb0154ca3c8f1c4305
Author(s)
Pankratova, Yanina
Hong, Mei
Date Issued
June 24, 2025
Journal
Biochemistry
Publisher
American Chemical Society
Citation
Side Chain Structures of the Proton-Selective Histidine and Gating Tryptophan in Influenza BM2 Reveal Both Conservation and Variation of the Proton Conduction Mechanism. Yanina Pankratova and Mei Hong. Biochemistry 2025 64 (14), 3081-3092.
Version
Author's final manuscript
Abstract
Aromatic residues play important roles in protein structure and function, but are difficult to study at atomic resolution by NMR because of their low spectral sensitivity and resolution. The M2 proton channels of influenza A and B viruses use a histidine for proton selection and a tryptophan for gating. High-resolution structures and dynamics of His37 and Trp41 side chains in AM2 have provided detailed insights into the proton conduction mechanism of AM2. However, the side chain structures of the corresponding His19 and Trp23 in BM2 have not been established. Here, we directly determine the side chain conformations of His19 and Trp23 using 13C–15N and 13C–19F distance measurements. Interestingly, we find that His19 adopts a distribution of χ1 torsion angles: the major conformer places the imidazole ring in a tilted and partly transverse orientation from the channel axis, while a minor population orients the imidazole ring parallel to the channel axis, similar to His37 in AM2. Trp23 adopts χ1 and χ2 angles similar to those of Trp41 in AM2, but the indole ring orientation inside the pore differs moderately from that of Trp41 due to backbone conformational differences. Finally, a membrane-surface histidine in BM2, His27, is dynamic, consistent with its distinct function from His19. These results provide new insights into the structural basis for the different proton conduction behaviors of influenza AM2 and BM2 and illustrate how interactions among aromatic residues influence the structure and function of membrane proteins.
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DOI of Published Version
https://doi.org/10.1021/acs.biochem.5c00242
