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Insight into structural diversity of influenza virus haemagglutinin

(2013) JOURNAL OF GENERAL VIROLOGY. 94. p.1712-1722
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Abstract
Influenza virus infects host cells through membrane fusion, a process mediated by the low pH-induced conformational change of the viral surface glycoprotein haemagglutinin (HA). We determined the structures and biochemical properties of the HA proteins from A/Korea/01/2009 (KR01), a 2009 pandemic strain, and A/Thailand/CU44/2006 (CU44), a seasonal strain. The crystal structure of KR01 HA revealed a V-shaped head-to-head arrangement, which is not seen in other HA proteins including CU44 HA. We isolated a broadly neutralizing H1-specific monoclonal antibody GC0757. The KR01 HA-Fab0757 complex structure also exhibited a head-to-head arrangement of HA. Both native and Fab complex structures reveal a different spatial orientation of HA1 relative to HA2, indicating that HA is flexible and dynamic at neutral pH. Further, the KR01 HA exhibited significantly lower protein stability and increased susceptibility to proteolytic cleavage compared with other HAs. Our structures provide important insights into the conformational flexibility of HA.
Keywords
SWINE-ORIGIN, PROTEOLYTIC ACTIVATION, MEMBRANE-FUSION, CRYSTAL-STRUCTURE, RECEPTOR-BINDING, PATHOGENESIS, PROTEIN, TRANSMISSION, FERRETS, HUMANS

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Citation

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MLA
Cho, Ki Joon, Ji-Hye Lee, Kwang W Hong, et al. “Insight into Structural Diversity of Influenza Virus Haemagglutinin.” JOURNAL OF GENERAL VIROLOGY 94 (2013): 1712–1722. Print.
APA
Cho, K. J., Lee, J.-H., Hong, K. W., Kim, S.-H., Park, Y., Lee, J. Y., Kang, S., et al. (2013). Insight into structural diversity of influenza virus haemagglutinin. JOURNAL OF GENERAL VIROLOGY, 94, 1712–1722.
Chicago author-date
Cho, Ki Joon, Ji-Hye Lee, Kwang W Hong, Se-Ho Kim, Yiho Park, Jun Young Lee, Seokha Kang, et al. 2013. “Insight into Structural Diversity of Influenza Virus Haemagglutinin.” Journal of General Virology 94: 1712–1722.
Chicago author-date (all authors)
Cho, Ki Joon, Ji-Hye Lee, Kwang W Hong, Se-Ho Kim, Yiho Park, Jun Young Lee, Seokha Kang, Sella Kim, Ji Hoon Yang, Eui-Ki Kim, Jong Hyeon Seok, Satoru Unzai, Sam Yong Park, Xavier Saelens, Chui-Joong Kim, Joo-Yeon Lee, Chun Kang, Hee-Bok Oh, Mi Sook Chung, and Kyung Hyun Kim. 2013. “Insight into Structural Diversity of Influenza Virus Haemagglutinin.” Journal of General Virology 94: 1712–1722.
Vancouver
1.
Cho KJ, Lee J-H, Hong KW, Kim S-H, Park Y, Lee JY, et al. Insight into structural diversity of influenza virus haemagglutinin. JOURNAL OF GENERAL VIROLOGY. 2013;94:1712–22.
IEEE
[1]
K. J. Cho et al., “Insight into structural diversity of influenza virus haemagglutinin,” JOURNAL OF GENERAL VIROLOGY, vol. 94, pp. 1712–1722, 2013.
@article{4128175,
  abstract     = {Influenza virus infects host cells through membrane fusion, a process mediated by the low pH-induced conformational change of the viral surface glycoprotein haemagglutinin (HA). We determined the structures and biochemical properties of the HA proteins from A/Korea/01/2009 (KR01), a 2009 pandemic strain, and A/Thailand/CU44/2006 (CU44), a seasonal strain. The crystal structure of KR01 HA revealed a V-shaped head-to-head arrangement, which is not seen in other HA proteins including CU44 HA. We isolated a broadly neutralizing H1-specific monoclonal antibody GC0757. The KR01 HA-Fab0757 complex structure also exhibited a head-to-head arrangement of HA. Both native and Fab complex structures reveal a different spatial orientation of HA1 relative to HA2, indicating that HA is flexible and dynamic at neutral pH. Further, the KR01 HA exhibited significantly lower protein stability and increased susceptibility to proteolytic cleavage compared with other HAs. Our structures provide important insights into the conformational flexibility of HA.},
  author       = {Cho, Ki Joon and Lee, Ji-Hye and Hong, Kwang W and Kim, Se-Ho and Park, Yiho and Lee, Jun Young and Kang, Seokha and Kim, Sella and Yang, Ji Hoon and Kim, Eui-Ki and Seok, Jong Hyeon and Unzai, Satoru and Park, Sam Yong and Saelens, Xavier and Kim, Chui-Joong and Lee, Joo-Yeon and Kang, Chun and Oh, Hee-Bok and Chung, Mi Sook and Kim, Kyung Hyun},
  issn         = {0022-1317},
  journal      = {JOURNAL OF GENERAL VIROLOGY},
  keywords     = {SWINE-ORIGIN,PROTEOLYTIC ACTIVATION,MEMBRANE-FUSION,CRYSTAL-STRUCTURE,RECEPTOR-BINDING,PATHOGENESIS,PROTEIN,TRANSMISSION,FERRETS,HUMANS},
  language     = {eng},
  pages        = {1712--1722},
  title        = {Insight into structural diversity of influenza virus haemagglutinin},
  url          = {http://dx.doi.org/10.1099/vir.0.051136-0},
  volume       = {94},
  year         = {2013},
}

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