Alpha2beta1 integrin recognition of the carboxyl-terminal propeptide of type I procollagen: integrin recognition and feed-back 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 extracellular matrix biosynthesis and that the propeptide bind to the alpha2beta1 integrin. This raises the intriguing hypothesis that the regulatory propeptide sequences exert their effects as a consequence of binding to the integrin. We show that recombinant alpha1(I) collagen chain C-terminal propeptide contains a binding site for the intact alpha2beta1 integrin and for a recombinant alpha2 integrin I domain, but not for the alpha1beta1 integrin, a structurally and functionally related collagen/laminin receptor. Additional studies employing a series of recombinant N-terminal and C-terminal deletion mutants, internal fragments of the propeptide, synthetic peptides, recombinant alpha2 integrin I domain and inhibitory monoclonal antibodies established that the previously identified sequences within the alpha1(I) C-terminal propeptide that mediate regulation of matrix biosynthesis are neither necessary nor sufficient for alpha2beta1 integrin binding. In contrast, the integrin recognition site is composed of a conformationally complex determinant located within a structurally distinct 115 amino acid region of the propeptide.
Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110-1093, USA.
M
M
Bhattacharyya-Pakrasi
S K
SK
Dickeson
S A
SA
Santoro
D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D003094:Collagen / Q000378:metabolism*; D004285:Dogs; D005109:Extracellular Matrix / Q000378:metabolism*; D016023:Integrins / Q000378:metabolism*; D011347:Procollagen / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D038981:Receptors, Collagen
D016023:Integrins; D011347:Procollagen; D038981:Receptors, Collagen; D003094:Collagen