title: Crystal structure of the collagen alpha1(VIII) NC1 trimer.
abstract: Collagen VIII is a major component of Descemet's membrane and is also found in vascular subendothelial matrices. The C-terminal non-collagenous domain (NC1) domain of collagen VIII, which is a member of the C1q-like protein family, forms a stable trimer and is thought to direct the assembly of the collagen triple helix, as well as polygonal supramolecular structures. We have solved the crystal structure of the mouse alpha1(VIII)(3) NC1 domain trimer at 1.9 A resolution. Each subunit of the intimate NC1 trimer consists of a ten-stranded beta-sandwich. The surface of the collagen VIII NC1 trimer presents three strips of partially exposed aromatic residues shown to interact with the non-ionic detergent CHAPS, which are likely to be involved in supramolecular assemblies. Equivalent strips exist in the NC1 domain of the closely related collagen X, suggesting a conserved assembly mechanism. Surprisingly, the collagen VIII NC1 trimer lacks the buried calcium cluster of the collagen X NC1 trimer. The mouse alpha1(VIII) and alpha2(VIII) NC1 domains are 71.5% identical in sequence, with the differences being concentrated on the NC1 trimer surface. A few non-conservative substitutions map to the subunit interfaces near the surface, but it is not obvious from the structure to what extent they determine the preferred assembly of collagen VIII alpha1 and alpha2 chains into homotrimers.
authors.affiliation: Department of Biological Sciences, Imperial College London, South Kensington Campus, London SW7 2AZ, UK.
authors.forename: Marc
authors.initials: M
authors.lastname: Kvansakul
authors.forename: Oren
authors.initials: O
authors.lastname: Bogin
authors.forename: Erhard
authors.initials: E
authors.lastname: Hohenester
authors.forename: Avner
authors.initials: A
authors.lastname: Yayon
mesh_terms: D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D024102:Collagen Type VIII / Q000737:chemistry* / Q000235:genetics; D024121:Collagen Type X / Q000737:chemistry; D003461:Crystallography; D051379:Mice; D008969:Molecular Sequence Data; D015394:Molecular Structure; D017434:Protein Structure, Tertiary
chemical_list: D024102:Collagen Type VIII; D024121:Collagen Type X