Effects of conformational activation of integrin alpha 1I and alpha 2I domains on selective recognition of laminin and collagen subtypes

A1 Journal article (refereed)


Internal Authors/Editors


Publication Details

List of Authors: Mira Tulla, Matti Lahti, J. Santeri Puranen, Anna-Maria Brandt, Jarmo Käpylä, Anna Domogatskaya, Tiina A.Salminen, Karl Tryggvason, Mark S.Johnson, Jyrki Heino
Publisher: ELSEVIER INC
Publication year: 2008
Journal: Experimental Cell Research
Journal acronym: EXP CELL RES
Volume number: 314
Issue number: 8
Start page: 1734
End page: 1743
Number of pages: 10
ISSN: 0014-4827
eISSN: 1090-2422


Abstract

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.


Keywords

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

Last updated on 2019-08-12 at 03:05