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

133 Citations (Scopus)

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

Fingerprint

Adenoviridae
Integrins
Cryoelectron Microscopy
Epitopes
Immunoglobulin Fab Fragments
Visualization
Immunoglobulin G
Viruses
Electron microscopy
Antibodies
Adenoviridae Infections
Human Adenoviruses
Virus Internalization
Molecules
Computer-Assisted Image Processing
Particle interactions
Neutralizing Antibodies
Image reconstruction
Cell Communication
Crystal structure

Keywords

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

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Stewart, P. L., Chiu, C. Y., Huang, S., Muir, T., Zhao, Y., Chait, B., ... 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

Cryo-EM visualization of an exposed RGD epitope on adenovirus that escapes antibody neutralization. / Stewart, Phoebe L.; Chiu, Charles Y.; Huang, Shuang; Muir, Tom; Zhao, Yingming; Chait, Brian; Mathias, Patricia; Nemerow, Glen R.

In: EMBO Journal, Vol. 16, No. 6, 17.03.1997, p. 1189-1198.

Research output: Contribution to journalArticle

Stewart, PL, Chiu, CY, Huang, S, Muir, T, Zhao, Y, Chait, B, Mathias, P & Nemerow, GR 1997, 'Cryo-EM visualization of an exposed RGD epitope on adenovirus that escapes antibody neutralization', EMBO Journal, vol. 16, no. 6, pp. 1189-1198. https://doi.org/10.1093/emboj/16.6.1189
Stewart, Phoebe L. ; Chiu, Charles Y. ; Huang, Shuang ; Muir, Tom ; Zhao, Yingming ; Chait, Brian ; Mathias, Patricia ; Nemerow, Glen R. / Cryo-EM visualization of an exposed RGD epitope on adenovirus that escapes antibody neutralization. In: EMBO Journal. 1997 ; Vol. 16, No. 6. pp. 1189-1198.
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