Inhibition of the human respiratory syncytial virus small hydrophobic protein and structural variations in a bicelle environment
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Other documents of the author: Li, Yan; To, Janet; Verdiá Báguena, Carmen; Dossena, Silvia; Surya, Wahyu; Huang, Mei; Paulmichl, Markus; Liu, Ding Xiang; Aguilella, Vicente; Torres, Jaume
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comunitat-uji-handle2:10234/2507
comunitat-uji-handle3:10234/6973
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http://dx.doi.org/10.1128/JVI.00839-14 |
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Title
Inhibition of the human respiratory syncytial virus small hydrophobic protein and structural variations in a bicelle environmentAuthor (s)
Date
2014Publisher
American Society for MicrobiologyISSN
0022-538X; 1098-5514Bibliographic citation
LI, Yan, et al. Inhibition of the human respiratory syncytial virus small hydrophobic protein and structural variations in a bicelle environment. Journal of virology, 2014, vol. 88, no 20, p. 11899-11914.Type
info:eu-repo/semantics/articlePublisher version
http://jvi.asm.org/content/88/20/11899.full.pdf+htmlVersion
info:eu-repo/semantics/publishedVersionSubject
Abstract
The small hydrophobic (SH) protein is a 64-amino-acid polypeptide encoded by the human respiratory syncytial virus (hRSV). SH protein has a single α-helical transmembrane (TM) domain that forms pentameric ion channels. ... [+]
The small hydrophobic (SH) protein is a 64-amino-acid polypeptide encoded by the human respiratory syncytial virus (hRSV). SH protein has a single α-helical transmembrane (TM) domain that forms pentameric ion channels. Herein, we report the first inhibitor of the SH protein channel, pyronin B, and we have mapped its binding site to a conserved surface of the RSV SH pentamer, at the C-terminal end of the transmembrane domain. The validity of the SH protein structural model used has been confirmed by using a bicellar membrane-mimicking environment. However, in bicelles the α-helical stretch of the TM domain extends up to His-51, and by comparison with previous models both His-22 and His-51 adopt an interhelical/lumenal orientation relative to the channel pore. Neither His residue was found to be essential for channel activity although His-51 protonation reduced channel activity at low pH, with His-22 adopting a more structural role. The latter results are in contrast with previous patch clamp data showing channel activation at low pH, which could not be reproduced in the present work. Overall, these results establish a solid ground for future drug development targeting this important viroporin. [-]
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Journal of virology, 2014, vol. 88, no 20Rights
© 2014, American Society for Microbiology.
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