Collagen IX: evidence for a structural association between NC4 domains in cartilage and a novel cleavage site in the alpha 1(IX) chain.

Collagen IX, a structural component of the extracellular matrix of connective tissues, is synthesized as long and short forms which contain or lack, respectively, a 27 kDa non-collagenous (NC) 4 domain at the N-terminus of the alpha 1(IX) chain of the molecule. The long form occurs in cartilage and developing cornea, but not in vitreous, suggesting a specialized function for the NC4 domain, perhaps by interacting with other macromolecules. To test this hypothesis, embryonic chick cartilage was treated with DTSSP, dissociated with bacterial collagenase, and the NC4-containing DTSSP-cross-linked protein complexes examined and purified. Analysis of cartilage extracts using an anti-NC4 antibody, and of purified NC4-containing complexes, identified a predominant NC4 dimer. A naturally-occurring N-terminal fragment of the alpha 1(IX) chain, whose size is equivalent to the NC4-COL3-NC3 domains of the chain, was identified. Association of collagen IX molecules via NC4 domains and the existence of a cleavage site close to the NC3 domain of the molecule are likely to be of primary importance in the growth and remodeling processes of cartilage, in health and disease.