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A Structure of a Collagen VI VWA Domain Displays N and C Termini at Opposite Sides of the Protein

DOI: 10.1016/j.str.2013.06.028 DOI Help

Authors: Ann-kathrin a Becker (University of Cologne) , Halina Mikolajek (University of Southampton) , Mats Paulsson (University of Cologne) , Raimund Wagener (University of Cologne) , Joern Werner (University of Southampton)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Structure , VOL 22 (2) , PAGES 199 - 208

State: Published (Approved)
Published: February 2014
Diamond Proposal Number(s): 8889

Open Access Open Access

Abstract: 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 Å 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.

Subject Areas: Biology and Bio-materials, Chemistry, Medicine


Instruments: I24-Microfocus Macromolecular Crystallography

Added On: 01/04/2015 16:22

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