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Integrin activation state determines selectivity for novel recognition sites in fibrillar collagens.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2004 Nov 12; Vol. 279 (46), pp. 47763-72. Date of Electronic Publication: 2004 Sep 03. - Publication Year :
- 2004
-
Abstract
- Only three recognition motifs, GFOGER, GLOGER, and GASGER, all present in type I collagen, have been identified to date for collagen-binding integrins, such as alpha(2)beta(1). Sequence alignment was used to investigate the occurrence of related motifs in other human fibrillar collagens, and located a conserved array of novel GER motifs within their triple helical domains. We compared the integrin binding properties of synthetic triple helical peptides containing examples of such sequences (GLSGER, GMOGER, GAOGER, and GQRGER) or the previously identified motifs. Recombinant inserted (I) domains of integrin subunits alpha(1), alpha(2) and alpha(11) all bound poorly to all motifs other than GFOGER and GLOGER. Similarly, alpha(2)beta(1) -containing resting platelets adhered well only to GFOGER and GLOGER, while ADP-activated platelets, HT1080 cells and two active alpha(2)I domain mutants (E318W, locked open) bound all motifs well, indicating that affinity modulation determines the sequence selectivity of integrins. GxO/SGER peptides inhibited platelet adhesion to collagen monomers with order of potency F >/= L >/= M > A. These results establish GFOGER as a high affinity sequence, which can interact with the alpha(2)I domain in the absence of activation and suggest that integrin reactivity of collagens may be predicted from their GER content.
- Subjects :
- Animals
Blood Platelets metabolism
Cell Line
Collagen Type I chemistry
Collagen Type I genetics
Humans
Integrin alpha Chains genetics
Integrin alpha Chains metabolism
Integrin alpha2beta1 genetics
Peptides chemistry
Peptides genetics
Platelet Adhesiveness physiology
Protein Binding
Protein Structure, Secondary
Protein Structure, Tertiary
Recombinant Fusion Proteins genetics
Recombinant Fusion Proteins metabolism
Sequence Alignment
Amino Acid Motifs
Collagen Type I metabolism
Integrin alpha2beta1 metabolism
Peptides metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9258
- Volume :
- 279
- Issue :
- 46
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 15345717
- Full Text :
- https://doi.org/10.1074/jbc.M404685200