The α4(IV) chain of basement membrane collagen: Isolation of cDNAS encoding bovine a4(IV) and comparison with other type IV collagens

Renal basement membranes are believed to contain five distinct type IV collagens. An understanding of the specific roles of these collagens and the specificities of their interactions will be aided by knowledge of their comparative structures. Genes for α1(IV), α2(IV), α3(IV), and α5(IV) have been cloned and the deduced peptide sequences compared. A fifth chain, α4(IV), has been identified in glomerular and other basement membranes. Using a polymerase chain reaction-based strategy and short known peptide sequences from the noncollagenous domain (NC1), we have cloned and characterized partial bovine cDNAs of α4(IV). Sequence analysis shows that this molecule has characteristic features of type IV collagens including an NH₂-terminal Gly-X-Y domain which is interrupted at several points and a COOH-terminal NC1 domain with 12 cysteine residues in positions identical to those of other type IV collagens. Within the NC1 domain bovine α4(IV) has 70, 59, 58, and 53% amino acid identity with human α2(IV), α1(IV), α5(IV), and α3(IV), respectively. Alignment of the peptides also shows that α4(IV) is most closely related to α2(IV). Nevertheless, in the extreme COOH-terminal region of the NC1 domain there are structural features that are unique to α4(IV). Cloning of the region of α4(IV) that encodes the NC1 domain allows comparison of all five type IV collagens and highlights certain regions that are likely to be important in the specificities of NC1-NC1 interactions and in other discriminant functions of these molecules.