A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Molecular mechanism of alpha 2 beta 1 integrin interaction with human echovirus 1
Tekijät: Jokinen J, White DJ, Salmela M, Huhtala M, Käpylä J, Sipila K, Puranen JS, Nissinen L, Kankaanpaa P, Marjomaki V, Hyypia T, Johnson MS, Heino J
Kustantaja: NATURE PUBLISHING GROUP
Julkaisuvuosi: 2010
Journal: EMBO Journal
Tietokannassa oleva lehden nimi: EMBO JOURNAL
Lehden akronyymi: EMBO J
Numero sarjassa: 1
Vuosikerta: 29
Numero: 1
Aloitussivu: 196
Lopetussivu: 208
Sivujen määrä: 13
ISSN: 0261-4189
DOI: https://doi.org/10.1038/emboj.2009.326
Tiivistelmä
Conformational activation increases the affinity of integrins to their ligands. On ligand binding, further changes in integrin conformation elicit cellular signalling. Unlike any of the natural ligands of alpha 2 beta 1 integrin, human echovirus 1 (EV1) seemed to bind more avidly a 'closed' than an activated 'open' form of the alpha 2I domain. Furthermore, a mutation E336A in the alpha 2 subunit, which inactivated alpha 2 beta 1 as a collagen receptor, enhanced alpha 2 beta 1 binding to EV1. Thus, EV1 seems to recognize an inactive integrin, and not even the virus binding could trigger the conformational activation of alpha 2 beta 1. This was supported by the fact that the integrin clustering by EV1 did not activate the p38 MAP kinase pathway, a signalling pathway that was shown to be dependent on E336-related conformational changes in alpha 2 beta 1. Furthermore, the mutation E336A did neither prevent EV1 induced and alpha 2 beta 1 mediated protein kinase C activation nor EV1 internalization. Thus, in its entry strategy EV1 seems to rely on the activation of signalling pathways that are dependent on alpha 2 beta 1 clustering, but do not require the conformational regulation of the receptor. The EMBO Journal (2010) 29, 196-208. doi: 10.1038/emboj.2009.326; Published online 19 November 2009
Conformational activation increases the affinity of integrins to their ligands. On ligand binding, further changes in integrin conformation elicit cellular signalling. Unlike any of the natural ligands of alpha 2 beta 1 integrin, human echovirus 1 (EV1) seemed to bind more avidly a 'closed' than an activated 'open' form of the alpha 2I domain. Furthermore, a mutation E336A in the alpha 2 subunit, which inactivated alpha 2 beta 1 as a collagen receptor, enhanced alpha 2 beta 1 binding to EV1. Thus, EV1 seems to recognize an inactive integrin, and not even the virus binding could trigger the conformational activation of alpha 2 beta 1. This was supported by the fact that the integrin clustering by EV1 did not activate the p38 MAP kinase pathway, a signalling pathway that was shown to be dependent on E336-related conformational changes in alpha 2 beta 1. Furthermore, the mutation E336A did neither prevent EV1 induced and alpha 2 beta 1 mediated protein kinase C activation nor EV1 internalization. Thus, in its entry strategy EV1 seems to rely on the activation of signalling pathways that are dependent on alpha 2 beta 1 clustering, but do not require the conformational regulation of the receptor. The EMBO Journal (2010) 29, 196-208. doi: 10.1038/emboj.2009.326; Published online 19 November 2009
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