Electron microscopy of antibody complexes of influenza virus haemagglutinin in the fusion pH conformation - PubMed (original) (raw)
Electron microscopy of antibody complexes of influenza virus haemagglutinin in the fusion pH conformation
S A Wharton et al. EMBO J. 1995.
Abstract
Activation of the membrane fusion potential of influenza haemagglutinin (HA) at endosomal pH requires changes in its structure. X-ray analysis of TBHA2, a proteolytic fragment of HA in the fusion pH conformation, indicates that at the pH of fusion the 'fusion peptide' is displaced by > 10 nm from its location in the native structure to the tip of an 11 nm triple-stranded coiled coil, and that the formation of this structure involves extensive re-folding or reorganization of HA. Here we examine the structure of TBHA2 with the electron microscope and compare it with the fusion pH structure of HA2 in virosomes, HA2 in aggregates formed at fusion pH by the soluble, bromelain-released ectodomain BHA and HA2 in liposomes with which BHA associates at fusion pH. We have oriented each HA2 preparation for comparison, using site-specific monoclonal antibodies. We conclude that the structural changes in membrane-anchored and soluble HA preparations at the pH of fusion appear to be the same; that in the absence of a target membrane, the 'fusion peptide' of HA in virosomes associates with the virosome membrane so that HA2 is membrane bound at both N- and C-termini, which implies that inversion of the re-folded HA can occur; and that the structural changes observed by X-ray analysis do not result from the proteolytic digestions used in the preparation of TBHA2.
Similar articles
- A soluble domain of the membrane-anchoring chain of influenza virus hemagglutinin (HA2) folds in Escherichia coli into the low-pH-induced conformation.
Chen J, Wharton SA, Weissenhorn W, Calder LJ, Hughson FM, Skehel JJ, Wiley DC. Chen J, et al. Proc Natl Acad Sci U S A. 1995 Dec 19;92(26):12205-9. doi: 10.1073/pnas.92.26.12205. Proc Natl Acad Sci U S A. 1995. PMID: 8618870 Free PMC article. - Studies on the structure of the influenza virus haemagglutinin at the pH of membrane fusion.
Ruigrok RW, Aitken A, Calder LJ, Martin SR, Skehel JJ, Wharton SA, Weis W, Wiley DC. Ruigrok RW, et al. J Gen Virol. 1988 Nov;69 ( Pt 11):2785-95. doi: 10.1099/0022-1317-69-11-2785. J Gen Virol. 1988. PMID: 3183628 - H+-induced membrane insertion of influenza virus hemagglutinin involves the HA2 amino-terminal fusion peptide but not the coiled coil region.
Durrer P, Galli C, Hoenke S, Corti C, Glück R, Vorherr T, Brunner J. Durrer P, et al. J Biol Chem. 1996 Jun 7;271(23):13417-21. doi: 10.1074/jbc.271.23.13417. J Biol Chem. 1996. PMID: 8662770 - Receptor binding and membrane fusion in virus entry: the influenza hemagglutinin.
Skehel JJ, Wiley DC. Skehel JJ, et al. Annu Rev Biochem. 2000;69:531-69. doi: 10.1146/annurev.biochem.69.1.531. Annu Rev Biochem. 2000. PMID: 10966468 Review. - Composition and functions of the influenza fusion peptide.
Cross KJ, Langley WA, Russell RJ, Skehel JJ, Steinhauer DA. Cross KJ, et al. Protein Pept Lett. 2009;16(7):766-78. doi: 10.2174/092986609788681715. Protein Pept Lett. 2009. PMID: 19601906 Review.
Cited by
- Hemagglutinin Stability Determines Influenza A Virus Susceptibility to a Broad-Spectrum Fusion Inhibitor Arbidol.
Li Z, Li T, Liu M, Ivanovic T. Li Z, et al. ACS Infect Dis. 2022 Aug 12;8(8):1543-1552. doi: 10.1021/acsinfecdis.2c00178. Epub 2022 Jul 12. ACS Infect Dis. 2022. PMID: 35819162 Free PMC article. - Relationship between hemagglutinin stability and influenza virus persistence after exposure to low pH or supraphysiological heating.
Yang G, Ojha CR, Russell CJ. Yang G, et al. PLoS Pathog. 2021 Sep 3;17(9):e1009910. doi: 10.1371/journal.ppat.1009910. eCollection 2021 Sep. PLoS Pathog. 2021. PMID: 34478484 Free PMC article. - The shape of pleomorphic virions determines resistance to cell-entry pressure.
Li T, Li Z, Deans EE, Mittler E, Liu M, Chandran K, Ivanovic T. Li T, et al. Nat Microbiol. 2021 May;6(5):617-629. doi: 10.1038/s41564-021-00877-0. Epub 2021 Mar 18. Nat Microbiol. 2021. PMID: 33737748 - Salinomycin Inhibits Influenza Virus Infection by Disrupting Endosomal Acidification and Viral Matrix Protein 2 Function.
Jang Y, Shin JS, Yoon YS, Go YY, Lee HW, Kwon OS, Park S, Park MS, Kim M. Jang Y, et al. J Virol. 2018 Nov 27;92(24):e01441-18. doi: 10.1128/JVI.01441-18. Print 2018 Dec 15. J Virol. 2018. PMID: 30282713 Free PMC article. - Atomistic simulations indicate the functional loop-to-coiled-coil transition in influenza hemagglutinin is not downhill.
Lin X, Noel JK, Wang Q, Ma J, Onuchic JN. Lin X, et al. Proc Natl Acad Sci U S A. 2018 Aug 21;115(34):E7905-E7913. doi: 10.1073/pnas.1805442115. Epub 2018 Jul 16. Proc Natl Acad Sci U S A. 2018. PMID: 30012616 Free PMC article.
References
- Virology. 1969 May;38(1):105-19 - PubMed
- Cell. 1985 Feb;40(2):431-9 - PubMed
- Nat New Biol. 1972 Aug 2;238(83):145-7 - PubMed
- Nature. 1981 Jan 29;289(5796):373-8 - PubMed
- Proc Natl Acad Sci U S A. 1982 Feb;79(4):968-72 - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
Miscellaneous