Integrin alpha v beta 3 binds a unique non-RGD site near the C-terminus of human tropoelastin.
Tropoelastin is the soluble precursor of the essential resilient connective tissue protein elastin. We examined the binding of integrin alpha(v)beta(3) to tropoelastin. In quantitative colorimetric solid-phase assays, purified alpha(v)beta(3) demonstrated saturable, divalent cation-dependent, single-site binding behavior on tropoelastin with a dissociation constant of 3.8 +/- 0.9 nM in the presence of 1 mM Mn(2+) which increased to 23 +/- 5 nM in the presence of 1 mM Ca(2+). Association with alpha(v)beta(3) was localized to the C-terminal 16 residues of tropoelastin, encompassing the region encoded by exon 36. This region comprises a unique disulfide loop in tropoelastin that is not essential for the interaction. This is the first identification of a specific, single binding site on tropoelastin and the first observation of direct binding of an integrin to a tropoelastin domain.
Rodgers
U R
UR
School of Molecular and Microbial Biosciences, University of Sydney, Building G08, Sydney, NSW 2006, Australia.
Weiss
Anthony S
AS
D001665:Binding Sites; D002118:Calcium / Q000494:pharmacology; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D008345:Manganese / Q000494:pharmacology; D009842:Oligopeptides; D011485:Protein Binding; D014333:Tropoelastin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D019096:Vitronectin / Q000378:metabolism
D039302:Integrin alphaVbeta3; D009842:Oligopeptides; D014333:Tropoelastin; D019096:Vitronectin; D008345:Manganese; C047981:arginyl-glycyl-aspartic acid; D002118:Calcium