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Publication Abstract from PubMed

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.

A structure of a collagen VI VWA domain displays N and C termini at opposite sides of the protein.,Becker AK, Mikolajek H, Paulsson M, Wagener R, Werner JM Structure. 2014 Feb 4;22(2):199-208. doi: 10.1016/j.str.2013.06.028. Epub 2013, Dec 12. PMID:24332716^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.