Cryo-EM visualization of an exposed RGD epitope on adenovirus that escapes antibody neutralization

Phoebe L. Stewart, Charles Y. Chiu, Shuang Huang, Tom Muir, Yingming Zhao, Brian Chait, Patricia Mathias, Glen R. Nemerow

Research output: Contribution to journalArticle

136 Scopus citations

Abstract

Interaction of the adenovirus penton base protein with α(v) integrins promotes virus entry into host cells. The location of the integrin binding sequence Arg-Gly-Asp (RGD) on human type 2 adenovirus (Ad2) was visualized by cryo-electron microscopy (cryo-EM) and image reconstruction using a mAb (DAV-1) which recognizes a linear epitope, IRGDTFATR. The sites for DAV-1 binding corresponded to the weak density above each of the five 22 Å protrusions on the adenovirus penton base protein. Modeling of a Fab fragment crystal structure into the adenovirus-Fab cryo-EM density indicated a large amplitude of motion for the Fab and the RGD epitope. An unexpected finding was that Fab fragments, but not IgG antibody molecules, inhibited adenovirus infection. Steric hindrance from the adenovirus fiber and a few bound IgG molecules, as well as epitope mobility, most likely prevent binding of IgG antibodies to all five RGD sites on the penton base protein within the intact virus. These studies indicate that the structure of the adenovirus particle facilitates interaction with cell integrins, whilst restricting binding of potentially neutralizing antibodies.

Original languageEnglish (US)
Pages (from-to)1189-1198
Number of pages10
JournalEMBO Journal
Volume16
Issue number6
DOIs
StatePublished - Mar 17 1997

Keywords

  • Adenovirus
  • Cryo-electron microscopy
  • Image reconstruction
  • Integrins
  • Neutralization

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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  • Cite this

    Stewart, P. L., Chiu, C. Y., Huang, S., Muir, T., Zhao, Y., Chait, B., Mathias, P., & Nemerow, G. R. (1997). Cryo-EM visualization of an exposed RGD epitope on adenovirus that escapes antibody neutralization. EMBO Journal, 16(6), 1189-1198. https://doi.org/10.1093/emboj/16.6.1189