Structure determination of an Fab fragment that neutralizes human rhinovirus 14 and analysis of the Fab-virus complex

Hansong Liu, Thomas Smith, Wai Ming Lee, Anne G. Mosser, Roland R. Rueckert, Norman H. Olson, R. Holland Cheng, Timothy S. Baker

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

The crystal structure of Pab17-IA, an antigen-binding fragment from a murine immunoglobulin that neutralizes human rhinovirus 14 (HRV14), has been solved to 2.7 Å resolution. Fab17-IA crystallized into three different space groups depending upon the method used to purify the intact antibody. The structure was determined by use of molecular and isomorphous replacement methods. The current model has a crystallographic R-factor of ~19% for 10,192 independent reflections between 8 and 2.7 Å. Correlation coefficient calculations showed that the Fab17-IA structure can be fit into the Fab17-IA/ HRV14 image reconstruction density to within 5 Å positional accuracy and to within a few degrees of rotation. The resulting interface of the docked antibody was examined and showed extensive charge and shape complementarity with the virus surface that was supported by site-directed mutagenesis experiments. The success of this approach validates the utility of combining X-ray crystallography with cryo-electron microscopy of complex macromolecular assemblies.

Original languageEnglish (US)
Pages (from-to)127-137
Number of pages11
JournalJournal of Molecular Biology
Volume240
Issue number2
DOIs
StatePublished - 1994
Externally publishedYes

Fingerprint

Rhinovirus
Immunoglobulin Fab Fragments
R388
Viruses
Macromolecular Substances
Cryoelectron Microscopy
Computer-Assisted Image Processing
Antibodies
X Ray Crystallography
Histocompatibility Antigens Class II
Site-Directed Mutagenesis
Immunoglobulins

Keywords

  • Crystallography
  • Fab-virus complex
  • Human rhinovirus
  • Immunoglobulin
  • Neutralization

ASJC Scopus subject areas

  • Virology

Cite this

Structure determination of an Fab fragment that neutralizes human rhinovirus 14 and analysis of the Fab-virus complex. / Liu, Hansong; Smith, Thomas; Lee, Wai Ming; Mosser, Anne G.; Rueckert, Roland R.; Olson, Norman H.; Cheng, R. Holland; Baker, Timothy S.

In: Journal of Molecular Biology, Vol. 240, No. 2, 1994, p. 127-137.

Research output: Contribution to journalArticle

Liu, Hansong ; Smith, Thomas ; Lee, Wai Ming ; Mosser, Anne G. ; Rueckert, Roland R. ; Olson, Norman H. ; Cheng, R. Holland ; Baker, Timothy S. / Structure determination of an Fab fragment that neutralizes human rhinovirus 14 and analysis of the Fab-virus complex. In: Journal of Molecular Biology. 1994 ; Vol. 240, No. 2. pp. 127-137.
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AU - Rueckert, Roland R.

AU - Olson, Norman H.

AU - Cheng, R. Holland

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