Construction of a model for the aggregation and cross-linking region (7S domain) of type IV collagen based upon an evaluation of the primary structure of the alpha 1 and alpha 2 chains in this region.

The amino acid sequence of the 212-residues-long N-terminal aggregation and cross-linking region of the alpha 2(IV) chain of human basement membrane collagen is presented. Comparing this with the primary structure of alpha 1(IV)7S [Glanville et al. (1985) Eur. J. Biochem. 152, 213-219] revealed a high degree of similar subdivisions in three functional regions. These are the 21-residue-long N-terminal non-triple-helical regions (NH1) containing cysteine and lysine residues which are putative cross-linking sites, a 117-residue-long triple-helical region (TH1) responsible for the aggregation of four molecules to form the 7S domain and which also possess cross-linking sites, and finally a 10-residue-long non-triple-helical region (NH2) which introduces the first of many flexible areas into the triple helical body of the molecule [Hofmann et al. (1984) J. Mol. Biol. 172, 325-343]. Computer calculations of interaction scores between parallel and antiparallelly aligned triple-helical regions (TH1) of the 7S domain allowed the prediction of a detailed model for the structure of the 7S complex which agreed well with models based primarily on electron micrographs of rotary shadowed type IV collagen tetramers. The results indicated that the assembly of the 7S domain is directed by hydrophobic interactions and is self-limiting to a tetramer. The most favourable chain configuration is alpha 2-alpha 1-alpha 1.