Collagens are major components of the extracellular matrices of all metazoan life and play crucial roles in developmental processes and tissue homeostasis. Collagens are composed of three polypeptide chains (α chains) that fold together to form the characteristic triple helical collagenous domain. Some types of triple helical protomers contain genetically identical α chains forming homotrimers, whereas others contain two or three different α chains forming heterotrimers. The sequences required to form a collagenous domain are Gly-X-Y repeats in which the X and Y positions are frequently proline and hydroxyproline. Glycine is required every third residue as it is the only amino acid small enough to pack into the central core of the triple helix. The triple helix-forming parts are surrounded by non-collagenous (NC) domains of variable sequence, size, and shape. Even if the triple helical parts represent the most striking feature of collagens, tissue specificity as well as defined binding of non-collagens seem to be encoded in the NC domains. The terminal NC domains are excised, modified, or incorporated directly into the final suprastructure, depending on protomer type and function [1,2].

Type IV collagen is one of the major constituents of basement membranes, a specialized form of extracellular matrix underlying epithelia that compartmentalizes tissues and provides molecular signals for influencing cell behavior. Each type IV chain contains a long triple-helical collagenous domain flanked by a short 7S domain of 25 residues and a globular non-collagenous NC1 domain of ~230 residues at the N- and C-terminus, respectively. In protomer assembly, the NC1 domains (monomers) of three chains interact, forming an NC1 trimer, to select and register chains for triple helix formation. In network assembly, the NC1 trimers of two protomers interact, forming a NC1 hexamer structure, to select and connect protomers [3,4,5].

The collagen IV NC1 domain contains 12 cysteines, and all of them are involved in disulfide bonds. It folds into a tertiary structure with predominantly β-strands (see <PDB:1LI1; A>). The collagen IV MC1 domain is composed of two similarly folded subdomains stabilized by 6 intrachain disulfide bonds involving the following pairs: C1-C6, C2-C5, C3-C4, C7-C12, C8-C11, and C9-C10. Each subdomain represents a compact disulfide-stabilized triangular structure, from which a finger-like hairpin loop projects into an incompletely formed six-stranded β-sheet of an adjacent subdomain of the same or of an adjacent chain clamping the subdomains tightly together [3,4,5].

The profile we developed covers the entire collagen IV NC1 domain.