a2Ct

Collagen I is the most abundant structural protein of connective tissues such as skin, bone, and tendon. This protein is first synthesized as a precursor molecule, procollagen I, that is characterized by the presence of a rod-like central triple-helical domain flanked by short linear telopeptides and globular N-terminal and C-terminal propeptides (1). Single procollagen I molecules are the building blocks for the biologically and mechanically relevant collagen fibrils. Formation of collagen fibrils is initiated by enzymatic cleavage of the N-terminal and the C-terminal propeptides. The N-terminal propeptides are cleaved by a group of enzymes that includes a disintegrin and metalloprotease with thrombospondin motifs (ADAMTS)-2,-3, and -14, whereas the C-terminal propeptides are cleaved by the metalloprotease bone morphogenetic protein 1 (BMP-1) and by the other members of a closely related family of mammalian tolloid-like metalloproteases (2-4). Such a removal of procollagen propeptides exposes telopeptides, which by engaging in site-specific intermolecular interactions drive collagen self-assembly.