ALPHA-2-BETA-1 INTEGRIN RECOGNITION OF THE CARBOXYL-TERMINAL PROPEPTIDE OF TYPE-I PROCOLLAGEN - INTEGRIN RECOGNITION AND FEEDBACK-REGULATION OF MATRIX BIOSYNTHESIS ARE MEDIATED BY DISTINCT SEQUENCES

It has recently been established that the carboxyl-terminal propeptide of type I collagen exert a feedback regulatory effect on extracellula r matrix biosynthesis and that the propeptide bind to the alpha(2)beta (1) integrin. This raises the intriguing hypothesis that the regulator y propeptide sequences exert their effects as a consequence of binding to the integrin. We show that recombinant alpha 1(I) collagen chain C -terminal propeptide contains a binding site for the intact alpha(2)be ta(1) integrin and for a recombinant alpha(2) integrin I domain, but n ot for the alpha(1)beta(1) integrin, a structurally and functionally r elated collagen/laminin receptor. Additional studies employing a serie s of recombinant N-terminal and C-terminal deletion mutants, internal fragments of the propeptide, synthetic peptides, recombinant alpha(2) integrin I domain and inhibitory monoclonal antibodies established tha t the previously identified sequences within the alpha 1(I) C-terminal propeptide that mediate regulation of matrix biosynthesis are neither necessary nor sufficient for alpha(2)beta(1) integrin binding. In con trast, the integrin recognition site is composed of a conformationally complex determinant located within a structurally distinct 115 amino acid region of the propeptide.