Effects of conformational activation of integrin α1I and α2I domains on selective recognition of laminin and collagen subtypes

Mira Tulla, Matti Lahti, J. Santeri Puranen, Anna-Maria Brandt, Jarmo Käpylä, Anna Domogatskaya, Tiina A. Salminen, Karl Tryggvason, Mark S. Johnson, Jyrki Heino

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Collagen receptor integrins alpha 1 beta 1 and alpha 2 beta 1 can selectively recognize different collagen subtypes. Here we show that their alpha I domains can discriminate between laminin isoforms as well: alpha 1I and alpha 2I recognized laminin-111, -211 and -511, whereas their binding to laminin-411 was negligible. Residue Arg-218 in alpha 1 was found to be instrumental in high-avidity binding. The gain-of-function mutation E318W makes the alpha 2I domain to adopt the "open" high-affinity conformation, while the wild-type alpha 2I domain favors the "closed" low-affinity conformation. The E318W mutation markedly increased alpha 2I domain binding to the laminins (-111, -211 and -511), leading us to propose that the activation state of the alpha 2 beta 1 integrin defines its role as a laminin receptor. However, neither wild-type nor alpha 2IE318W domain could bind to laminin-411. alpha 2IE318W also bound tighter to all collagens than alpha 2I wild-type, but it showed reduced ability to discriminate between collagens I, IV and IX. The corresponding mutation, E317A, in the alpha 1I domain transformed the domain into a high-avidity binder of collagens I and IV. Thus, our results indicate that conformational activation of integrin alpha 1I and alpha 2I domains leads to high-avidity binding to otherwise disfavoured Collagen subtypes. (C) 2008 Elsevier Inc. All rights reserved.
Original languageUndefined/Unknown
Pages (from-to)1734–1743
Number of pages10
JournalExperimental Cell Research
Issue number8
Publication statusPublished - May 2008
MoE publication typeA1 Journal article-refereed


  • integrin alpha I domain
  • integrin activation
  • ligand selectivity
  • laminin

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