Structural and Functional Analysis of Integrin α2I Domain Interaction with Echovirus 1

Li Xing, Mikko Huhtala, Vilja Pietiäinen, Jarmo Käpylä, Kirsi Vuorinen, Varpu Marjomäki, Jyrki Heino, Mark S. Johnson, Timo Hyypiä, R. Holland Cheng

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49 Scopus citations

Abstract

Integrins are cell surface receptors for several microbial pathogens including echovirus 1 (EV1), a picornavirus. Cryo-electron microscopy revealed that the functional domain (α2I) of human α 2β1 integrin binds to a surface depression on the EV1 capsid. This three-dimensional structure of EV1 bound to α 2I domain provides the first structural details of an integrin interacting with a picornavirus. The model indicates that α 2β1 integrin cannot simultaneously bind both EV1 and the physiological ligand collagen. Compared with collagen binding to the α2I domain, the virus binds with a 10-fold higher affinity but in vitro uncoating of EV1 was not observed as a result of attachment of α2I. A molecular model, constructed on the basis of the EV1-integrin complex, shows that multiple α2β1 heterodimers can bind at adjacent sites around the virus 5-fold symmetry axes without steric hindrance. In agreement with this, virus attachment to α2β1 integrin on the cell surface was found to result in integrin clustering, which can give rise to signaling and facilitate the initiation of the viral entry process that takes place via caveolae-mediated endocytosis.

Original languageEnglish (US)
Pages (from-to)11632-11638
Number of pages7
JournalJournal of Biological Chemistry
Volume279
Issue number12
DOIs
StatePublished - Mar 19 2004

ASJC Scopus subject areas

  • Biochemistry

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    Xing, L., Huhtala, M., Pietiäinen, V., Käpylä, J., Vuorinen, K., Marjomäki, V., Heino, J., Johnson, M. S., Hyypiä, T., & Cheng, R. H. (2004). Structural and Functional Analysis of Integrin α2I Domain Interaction with Echovirus 1. Journal of Biological Chemistry, 279(12), 11632-11638. https://doi.org/10.1074/jbc.M312441200