HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 278, Issue 28, 26208-26215, July 11, 2003

This Article Full Text Full Text (PDF) All Versions of this Article: 278/28/26208    most recent M301492200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Howitt, J. Articles by Freimuth, P. Search for Related Content PubMed PubMed Citation Articles by Howitt, J. Articles by Freimuth, P. Social Bookmarking                      What's this?

Structural Basis for Variation in Adenovirus Affinity for the Cellular Coxsackievirus and Adenovirus Receptor^*

Jason Howitt , Maria C. Bewley, Vito Graziano, John M. Flanagan and Paul Freimuth 

From the Biology Department, Brookhaven National Laboratory, Upton, New York 11973

The majority of adenovirus serotypes can bind to the coxsackievirus and adenovirus receptor (CAR) on human cells despite only limited conservation of the amino acid residues that comprise the receptor-binding sites of these viruses. Using a fluorescence anisotropy-based assay, we determined that the recombinant knob domain of the fiber protein from adenovirus serotype (Ad) 2 binds the soluble, N-terminal domain (domain 1 (D1)) of CAR with 8-fold greater affinity than does the recombinant knob domain from Ad12. Homology modeling predicted that the increased affinity of Ad2 knob for CAR D1 could result from additional contacts within the binding interface contributed by two residues, Ser⁴⁰⁸ and Tyr⁴⁷⁷, which are not conserved in the Ad12 knob. Consistent with this structural model, substitution of serine and tyrosine for the corresponding residues in the Ad12 knob (P417S and S489Y) increased the binding affinity by 4- and 8-fold, respectively, whereas the double mutation increased binding affinity 10-fold. X-ray structure analysis of Ad12 knob mutants P417S and S489Y indicated that both substituted residues potentially could form additional hydrogen bonds across the knob-CAR interface. Structural changes resulting from these mutations were highly localized, implying that the high tolerance for surface variation conferred by the stable knob scaffold can minimize the impact of antigenic drift on binding specificity and affinity during evolution of virus serotypes. Our results suggest that the interaction of knob domains from different adenovirus serotypes with CAR D1 can be accurately modeled using the Ad12 knob-CAR D1 crystal structure as a template.

Received for publication, February 11, 2003 , and in revised form, April 15, 2003.

^* This work was supported by Grant R01-AI36251 from the United States Public Health Service and by a grant from the United States Department of Energy Office of Biological and Environmental Research under Contract DE-AC02-98CH10886. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Present address: Dept. of Biological Sciences, Biophysics Section, Blackett Laboratory, Imperial College London, Prince Consort Road, London SW7 2BW, UK.

To whom correspondence should be addressed: Biology Dept., Brookhaven National Laboratory, Upton, NY 11973. Tel.: 631-344-3350; Fax: 631-344-3407; E-mail: freimuth{at}bnl.gov.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				N. M. Beach, R. B. Duncan, C. T. Larsen, X.-J. Meng, N. Sriranganathan, and F. W. Pierson Comparison of 12 turkey hemorrhagic enteritis virus isolates allows prediction of genetic factors affecting virulence J. Gen. Virol., August 1, 2009; 90(8): 1978 - 1985. [Abstract] [Full Text] [PDF]

				W. C. Russell Adenoviruses: update on structure and function J. Gen. Virol., January 1, 2009; 90(1): 1 - 20. [Abstract] [Full Text] [PDF]

				E. Seiradake, H. Lortat-Jacob, O. Billet, E. J. Kremer, and S. Cusack Structural and Mutational Analysis of Human Ad37 and Canine Adenovirus 2 Fiber Heads in Complex with the D1 Domain of Coxsackie and Adenovirus Receptor J. Biol. Chem., November 3, 2006; 281(44): 33704 - 33716. [Abstract] [Full Text] [PDF]

				E. Seiradake and S. Cusack Crystal Structure of Enteric Adenovirus Serotype 41 Short Fiber Head J. Virol., November 15, 2005; 79(22): 14088 - 14094. [Abstract] [Full Text] [PDF]

				M. Marttila, D. Persson, D. Gustafsson, M. K. Liszewski, J. P. Atkinson, G. Wadell, and N. Arnberg CD46 Is a Cellular Receptor for All Species B Adenoviruses except Types 3 and 7 J. Virol., November 15, 2005; 79(22): 14429 - 14436. [Abstract] [Full Text] [PDF]

				Y. Zhang and J. M. Bergelson Adenovirus Receptors J. Virol., October 1, 2005; 79(19): 12125 - 12131. [Full Text] [PDF]

				M. Qin, B. Escuadro, M. Dohadwala, S. Sharma, and R. K. Batra A Novel Role for the Coxsackie Adenovirus Receptor in Mediating Tumor Formation by Lung Cancer Cells Cancer Res., September 15, 2004; 64(18): 6377 - 6380. [Abstract] [Full Text] [PDF]

				W. P. Burmeister, D. Guilligay, S. Cusack, G. Wadell, and N. Arnberg Crystal Structure of Species D Adenovirus Fiber Knobs and Their Sialic Acid Binding Sites J. Virol., July 15, 2004; 78(14): 7727 - 7736. [Abstract] [Full Text] [PDF]

				V. Awasthi, G. Meinken, K. Springer, S. C. Srivastava, and P. Freimuth Biodistribution of Radioiodinated Adenovirus Fiber Protein Knob Domain after Intravenous Injection in Mice J. Virol., June 15, 2004; 78(12): 6431 - 6438. [Abstract] [Full Text] [PDF]