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https://hdl.handle.net/10356/100387
Title: | Inhibition of the human respiratory syncytial virus small hydrophobic protein and structural variations in a bicelle environment | Authors: | Li, Yan To, Janet Verdià-Baguena, Carmina Dossena, Silvia Surya, Wahyu Huang, Mei Paulmichi, Markus Liu, Ding Xiang Aguilella, Vicente M. Torres, Jaume |
Keywords: | DRNTU::Science::Biological sciences | Issue Date: | 2014 | Source: | Li, Y., To, J., Verdià-Baguena, C., Dossena, S., Surya, W., Huang, M., et al. (2014). Inhibition of the human respiratory syncytial virus small hydrophobic protein and structural variations in a bicelle environment. Journal of virology, 88(20), 11899-11914. | Series/Report no.: | Journal of virology | 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. 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. | URI: | https://hdl.handle.net/10356/100387 http://hdl.handle.net/10220/25717 |
DOI: | 10.1128/JVI.00839-14 | Rights: | © 2014 American Society for Microbiology. This paper was published in Journal of Virology and is made available as an electronic reprint (preprint) with permission of American Society for Microbiology. The paper can be found at the following official DOI: [http://dx.doi.org/10.1128/JVI.00839-14]. One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper is prohibited and is subject to penalties under law. | Fulltext Permission: | open | Fulltext Availability: | With Fulltext |
Appears in Collections: | SBS Journal Articles |
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