| First Author | Becker AK | Year | 2014 |
| Journal | Structure | Volume | 22 |
| Issue | 2 | Pages | 199-208 |
| PubMed ID | 24332716 | Mgi Jnum | J:389802 |
| Mgi Id | MGI:8393981 | Doi | 10.1016/j.str.2013.06.028 |
| Citation | Becker AK, et al. (2014) A structure of a collagen VI VWA domain displays N and C termini at opposite sides of the protein. Structure 22(2):199-208 |
| abstractText | Von Willebrand factor A (VWA) domains are versatile protein interaction domains with N and C termini in close proximity placing spatial constraints on overall protein structure. The 1.2 A crystal structures of a collagen VI VWA domain and a disease-causing point mutant show C-terminal extensions that place the N and C termini at opposite ends. This allows a "beads-on-a-string" arrangement of multiple VWA domains as observed for ten N-terminal domains of the collagen VI alpha3 chain. The extension is linked to the core domain by a salt bridge and two hydrophobic patches. Comparison of the wild-type and a muscular dystrophy-associated mutant structure identifies a potential perturbation of a protein interaction interface and indeed, the secretion of mutant collagen VI tetramers is affected. Homology modeling is used to locate a number of disease-associated mutations and analyze their structural impact, which will allow mechanistic analysis of collagen-VI-associated muscular dystrophy phenotypes. |
