Antibody-mediated neutralization of human rhinovirus 14 explored by means of cryoelectron microscopy and X-ray crystallography of virus-Fab complexes

Zhiwei Che, Norman H. Olson, Donna Leippe, Wai Ming Lee, Anne G. Mosser, Roland R. Rueckert, Timothy S. Baker, Thomas Smith

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

The structures of three different human rhinovirus 14 (HRV14)-Fab complexes have been explored with X-ray crystallography and cryoelectron microscopy procedures. All three antibodies bind to the NIm-IA site of HRV14, which is the β-β-β-C loop of the vital capsid protein VP1. Two antibodies, Fab17-IA (Fab17) and Fab12-IA (Fab12), bind bivalently to the virion surface and strongly neutralize vital infectivity whereas Fab1-IA (Fab1) strongly aggregates and weakly neutralizes virions. The structures of the two classes of virion-Fab complexes clearly differ and correlate with observed binding neutralization differences. Fab17 and Fab12 bind in essentially identical, tangential orientations to the viral surface, which favors bidentate binding over icosahedral twofold axes. Fab1 binds in a more radial orientation that makes bidentate binding unlikely. Although the binding orientations of these two antibody groups differ, nearly identical charge interactions occur at all paratope-epitope interfaces. Nucleotide sequence comparisons suggest that Fab17 and Fab12 are from the same progenitor cell and that some of the differing residues contact the south wall of the receptor binding canyon that encircles each of the icosahedral fivefold vertices. All of the antibodies contact a significant proportion of the canyon region and directly overlap much of the receptor (intercellular adhesion molecule 1 [ICAM-1]) binding site. Fab1, however, does not contact the same residues on the upper south wall (the side facing away from fivefold axes) at the receptor binding region as do Fab12 and Fab17. All three antibodies cause some stabilization of HRV14 against pH-induced inactivation; thus, stabilization may be mediated by invariant contacts with the canyon.

Original languageEnglish (US)
Pages (from-to)4610-4622
Number of pages13
JournalJournal of Virology
Volume72
Issue number6
StatePublished - Jun 1998
Externally publishedYes

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Human rhinovirus
Cryoelectron Microscopy
Rhinovirus
X Ray Crystallography
X-ray diffraction
neutralization
Viruses
canyons
viruses
antibodies
virion
Antibodies
Virion
receptors
Antibody Binding Sites
Capsid Proteins
protein aggregates
Intercellular Adhesion Molecule-1
coat proteins
epitopes

ASJC Scopus subject areas

  • Immunology

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Antibody-mediated neutralization of human rhinovirus 14 explored by means of cryoelectron microscopy and X-ray crystallography of virus-Fab complexes. / Che, Zhiwei; Olson, Norman H.; Leippe, Donna; Lee, Wai Ming; Mosser, Anne G.; Rueckert, Roland R.; Baker, Timothy S.; Smith, Thomas.

In: Journal of Virology, Vol. 72, No. 6, 06.1998, p. 4610-4622.

Research output: Contribution to journalArticle

Che, Zhiwei ; Olson, Norman H. ; Leippe, Donna ; Lee, Wai Ming ; Mosser, Anne G. ; Rueckert, Roland R. ; Baker, Timothy S. ; Smith, Thomas. / Antibody-mediated neutralization of human rhinovirus 14 explored by means of cryoelectron microscopy and X-ray crystallography of virus-Fab complexes. In: Journal of Virology. 1998 ; Vol. 72, No. 6. pp. 4610-4622.
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abstract = "The structures of three different human rhinovirus 14 (HRV14)-Fab complexes have been explored with X-ray crystallography and cryoelectron microscopy procedures. All three antibodies bind to the NIm-IA site of HRV14, which is the β-β-β-C loop of the vital capsid protein VP1. Two antibodies, Fab17-IA (Fab17) and Fab12-IA (Fab12), bind bivalently to the virion surface and strongly neutralize vital infectivity whereas Fab1-IA (Fab1) strongly aggregates and weakly neutralizes virions. The structures of the two classes of virion-Fab complexes clearly differ and correlate with observed binding neutralization differences. Fab17 and Fab12 bind in essentially identical, tangential orientations to the viral surface, which favors bidentate binding over icosahedral twofold axes. Fab1 binds in a more radial orientation that makes bidentate binding unlikely. Although the binding orientations of these two antibody groups differ, nearly identical charge interactions occur at all paratope-epitope interfaces. Nucleotide sequence comparisons suggest that Fab17 and Fab12 are from the same progenitor cell and that some of the differing residues contact the south wall of the receptor binding canyon that encircles each of the icosahedral fivefold vertices. All of the antibodies contact a significant proportion of the canyon region and directly overlap much of the receptor (intercellular adhesion molecule 1 [ICAM-1]) binding site. Fab1, however, does not contact the same residues on the upper south wall (the side facing away from fivefold axes) at the receptor binding region as do Fab12 and Fab17. All three antibodies cause some stabilization of HRV14 against pH-induced inactivation; thus, stabilization may be mediated by invariant contacts with the canyon.",
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