Previous Article | Next Article ![]()
Journal of Virology, August 2001, p. 7210-7214, Vol. 75, No. 15
Department of Respiratory Medicine and
Allergy, The Guy's, King's College and St. Thomas' Hospitals School
of Medicine, Guy's Hospital, London SE1 9RT,1
and The Randall Centre, King's College London, London SE1
1UL,3 United Kingdom, and GenVec,
Gaithersburg, Maryland 208782
Received 25 August 2000/Accepted 16 April 2001
The coxsackie B virus and adenovirus (Ad) receptor (CAR) functions
as an attachment receptor for multiple Ad serotypes. Here we show that
the Ad serotype 9 (Ad9) fiber knob binds to CAR with much reduced
affinity compared to the binding by Ad5 and Ad12 fiber knobs as well as
the knob of the long fiber of Ad41 (Ad41L). Substitution of Asp222 in
Ad9 fiber knob with a lysine that is conserved in Ad5, Ad12, and Ad41L
substantially improved Ad9 fiber knob binding to CAR, while the
corresponding substitution in Ad5 (Lys442Asp) significantly reduced Ad5
binding. The presence of an aspartic acid residue in Ad9 therefore
accounts, at least in part, for the reduced CAR binding affinity of the
Ad9 fiber knob. Site-directed mutagenesis of CAR revealed that CAR
residues Leu73 and Lys121 and/or Lys123 are critical contact residues,
with Tyr80 and Tyr83 being peripherally involved in the binding
interaction with the Ad5, Ad9, Ad12, and Ad41L fiber knobs. The overall
affinities and the association and dissociation rate constants for
wild-type CAR as well as Tyr80 and Tyr83 CAR mutants differed between
the serotypes, indicating that their binding modes, although similar, are not identical.
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.15.7210-7214.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Adenovirus Type 9 Fiber Knob Binds to the Coxsackie
B Virus-Adenovirus Receptor (CAR) with Lower Affinity than Fiber Knobs
of Other CAR-Binding Adenovirus Serotypes
*
Corresponding author. Mailing address: Department of
Respiratory Medicine & Allergy, The Guy's, King's College and St.
Thomas' Hospitals School of Medicine, 5th Floor, Thomas Guy House,
Guy's Hospital, St. Thomas St., London SE1 9RT, United Kingdom. Phone: 44-20-79552758. Fax: 44-20-74038640. E-mail:
george.santis{at}kcl.ac.uk.
This article has been cited by other articles:
| J. Bacteriol. | Mol. Cell. Biol. | Microbiol. Mol. Biol. Rev. |
|---|
| Clin. Vaccine Immunol. | ALL ASM JOURNALS |
|---|