2024-03-28T08:07:23Zhttps://repositori.uji.es/oai/requestoai:repositori.uji.es:10234/1307532024-03-26T08:28:50Zcom_10234_2507com_10234_9col_10234_6973
00925njm 22002777a 4500
dc
Li, Yan
author
To, Janet
author
Verdiá Báguena, Carmen
author
Dossena, Silvia
author
Surya, Wahyu
author
Huang, Mei
author
Paulmichl, Markus
author
Liu, Ding Xiang
author
Aguilella, Vicente
author
Torres, Jaume
author
2014
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.
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.
0022-538X
1098-5514
http://hdl.handle.net/10234/130753
http://dx.doi.org/10.1128/JVI.00839-14
small hydrophobic protein
histidine 22
histidine 51
pyronine
virus protein
Inhibition of the human respiratory syncytial virus small hydrophobic protein and structural variations in a bicelle environment