Functions of Integrin a 2B 1, A Collagen Receptor, in the Internalization of Echovirus 1 - Structure-Based Study of Viral Replication - page 63

Chapter 3

α 2β 1

Functions of Integrin , A Collagen

Receptor, in the Internalization of
Echovirus 1

Varpu Marjomäki * , Mikko Huhtala † , Mikko
Karjalainen * , Timo Hyypiä ‡ and Jyrki Heino §

α2β1 is a collagen-binding integrin that has been found to act as a receptor

for echovirus 1 (EV1), a picornavirus and a human pathogen. Integrin

α 2β1

binds EV1 and the natural ligands with a special inserted domain ( α I domain)

subunit. Molecular modeling based on a cryo EM structure
suggests that the exact binding sites are distinct but close enough to make
simultaneous binding impossible. Binding of EV1 to the integrins causes a
rapid clustering of the receptors on the plasma membrane, their internaliza-
tion in complex with the virus and gradual accumulation into cytoplasmic
caveosomes. The clustering is accompanied by rapid activation of protein
kinase C

in the integrin α

, which is necessary for the internalization process. Confocal and
electron microscopy have shown the presence of large complex tubulovesicu-
lar caveosomes containing both EV1 and

α

integrin. The caveosomal
nature of these structures has been verified by the accumulation of SV40 and
EV1 in the same caveolin-1 enriched structures, and the lack of classical endo-
somal markers. Viral RNA may be released directly from the caveosomes to

α2β 1

*Department of Biological and Environmental Sciences, University of Jyväskylä, Survontie 9,
FI-40500 Jyväskylä, Finland; E-mail: [e-mail]
† Department of Biochemistry, Åbo Akademi University, Tykistökatu 6A, FI-20520 Turku,
Finland; E-mail: [e-mail]
‡ Department Virology, University of Turku, Kiinamyllynkatu 13, FI-20520 Turku, Finland;
E-mail: [e-mail]
§ Department of Biochemistry and Food Chemistry, University of Turku, Vatselankatu 2, FI-20014
Turku, Finland; E-mail: [e-mail]

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