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Journal of Biomedicine and Biotechnology
Volume 2010, Article ID 541939, 7 pages
http://dx.doi.org/10.1155/2010/541939
Research Article

The Adenovirus Type 3 Dodecahedron's RGD Loop Comprises an HSPG Binding Site That Influences Integrin Binding

E. Gout,1,2,3 G. Schoehn,1,2,3,4 D. Fenel,1,2,3 H. Lortat-Jacob,1,2,3 and P. Fender1,2,3,4

1CNRS-Institut de Biologie Structurale, 41 rue Jules Horowitz, 38027 Grenoble, France
2CEA-Institut de Biologie Structurale, 41 rue Jules Horowitz, 38027 Grenoble, France
3UJF-Institut de Biologie Structurale, 41 rue Jules Horowitz, 38027 Grenoble, France
4Unit for Virus Host Cell Interaction UMI 3265, 6 rue Jules Horowitz, 38042 Grenoble Cedex 09, France

Received 1 October 2009; Accepted 17 December 2009

Academic Editor: Gerald Schumann

Copyright © 2010 E. Gout et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Human type 3 adenovirus dodecahedron (a virus like particle made of twelve penton bases) features the ability to enter cells through Heparan Sulphate Proteoglycans (HSPGs) and integrins interaction and is used as a versatile vector to deliver DNA or proteins. Cryo-EM reconstruction of the pseudoviral particle with Heparan Sulphate (HS) oligosaccharide shows an extradensity on the RGD loop. A set of mutants was designed to study the respective roles of the RGD sequence (RGE mutant) and of a basic sequence located just downstream. Results showed that the RGE mutant binding to the HS deficient CHO-2241 cells was abolished and unexpectedly, mutation of the basic sequence (KQKR to AQAS) dramatically decreased integrin recognition by the viral pseudoparticle. This basic sequence is thus involved in integrin docking, showing a close interplay between HSPGs and integrin receptors.