alphaVbeta6 is a novel receptor for human fibrillin-1. Comparative studies of molecular determinants underlying integrin-rgd affinity and specificity.

Journal article

Human fibrillin-1, the major structural protein of connective tissue 10-12 nm microfibrils, contains multiple calcium binding epidermal growth factor-like domains interspersed with transforming growth factor beta-binding protein-like (TB) domains. TB4 contains a flexible RGD loop that mediates cell adhesion via alphaVbeta3 and alpha5beta1 integrins. This study identifies integrin alphaVbeta6 as a novel cellular receptor for fibrillin-1 with a K(d) of approximately 0.45 mum. Analyses of this interaction by surface plasmon resonance and immunocytochemistry reveal different module requirements for alphaVbeta6 activation compared with those of alphaVbeta3, suggesting that a covalent linkage of an N-terminal calcium binding epidermal growth factor-like domain to TB4 can modulate alphaV integrin binding specificity. Furthermore, our data suggest alpha5beta1 is a low affinity fibrillin-1 receptor (K(d) > 1 mum), thus providing a molecular explanation for the different alpha5beta1 distribution patterns seen when human keratinocytes and fibroblasts are plated on recombinant fibrillin fragments versus those derived from the physiological ligand fibronectin. Non-focal contact distribution of alpha5beta1 suggests that its engagement by fibrillin-1 may elicit a lesser degree and/or different type of intracellular signaling compared with that seen with a high affinity ligand.

Authors: Jovanovic, J; Takagi, J; Choulier, L; Abrescia, N; Stuart, D

• Publication status: Published
• Journal: Journal of biological chemistry
• Volume: 282
• Issue: 9
• Pages: 6743-6751
• Publication date: 2007-03-01
• DOI: 10.1074/jbc.m607008200
• EISSN: 1083-351X
• ISSN: 0021-9258
• Language: English
• Keywords: Integrin alpha5beta1; Antigens, Neoplasm; Binding Sites; Microfilament Proteins; Integrins; Surface Plasmon Resonance; Peptide Fragments; Integrin alphaVbeta3; Humans; Protein Binding; Fibronectins