Structure
Volume 7, Issue 12, January 1999, Pages 1527-1538
Journal home page for Structure

Research Article
The crystal structure of coxsackievirus A9: new insights into the uncoating mechanisms of enteroviruses

https://doi.org/10.1016/S0969-2126(00)88343-4Get rights and content
Under an Elsevier user license
open archive

Abstract

Background: Coxsackievirus A9 (CAV9), a human pathogen causing symptoms ranging from common colds to fatal infections of the central nervous system, is an icosahedral single-stranded RNA virus that belongs to the genus Enterovirus of the family Picornaviridae. One of the four capsid proteins, VP1, includes the arginine-glycine-aspartate (RGD) motif within its C-terminal extension. This region binds to integrin αvβ3, the only receptor for CAV9 to be conclusively identified to date.

Results: The crystal structure of CAV9 in complex with the antiviral compound WIN 51711 has been solved to 2.9 Å resolution. The structures of the four capsid proteins, VP1 to VP4, resemble those of other picornaviruses. The antiviral compound is bound in the VP1 hydrophobic pocket, and it is possible that the pocket entrance contains a second WIN 51711 molecule. Continuous electron density for the VP1 N terminus provides a complete picture of the structure close to the fivefold axis. The VP1 C-terminal portion is on the outer surface of the virus and becomes disordered five-residues N-terminal to the RGD motif.

Conclusions: The RGD motif is exposed and flexible in common with other known integrin ligands. Although CAV9 resembles coxsackie B viruses (CBVs), several substitutions in the areas implicated in CBV receptor attachment suggest it may recognise a different receptor. The structure along the fivefold axis provides new information on the uncoating mechanism of enteroviruses. CAV9 might bind a larger natural pocket factor than other picornaviruses, an observation of particular relevance to the design of new antiviral compounds.

Keywords

picornavirus structure
RGD
uncoating
virus–receptor interaction
WIN compound

Cited by (0)

E Hendry, H Hatanaka, E Fry, M Smyth and J Tate, Laboratory of Molecular Biophysics, South Parks Road, Oxford OX1 3QU, UK.

G Stanway, Department of Biological Sciences, University of Essex, Colchester CO4 3SQ, UK.

J Santti and M Maaronen, Department of Virology, University of Turku, FIN-20520, Turku, Finland.

T Hyypiä, Department of Virology, University of Turku, FIN-20520, Turku, Haartman Institute, Department of Virology, University of Helsinki, FIN-00014, Helsinki, Finland.

D Stuart, Laboratory of Molecular Biophysics, OX1 3QU, Oxford Centre for Molecular Sciences, South Parks Road, Oxford, OX1 3QT, UK.

Present address for E Hendry: Centre for Biomolecular Sciences, University of St Andrews, North Haugh, St Andrews KY16 9ST, UK.

Present address for H Hatanaka, E Fry and D Stuart: Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK.

Present address for M Smyth: Department of Biochemistry, University of Leicester, Leicester LE1 7RH, UK.

Present address for J Tate: San Diego Supercomputer Center, University of California, San Diego, CA 92093-0537, USA.

E Hendry and H Hatanaka authors contributed equally to this work.

E-mail address for D Stuart (corresponding author): [email protected].