A structure of a collagen VI VWA domain displays N and C termini at opposite sides of the protein
A structure of a collagen VI VWA domain displays N and C termini at opposite sides of the protein
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 ?3 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.
199-208
Becker, Ann-Kathrin A.
a2e4106f-21b5-4cb1-a861-2add4c906fa5
Mikolajek, Halina
c394c255-9248-4217-ace9-4a0382bfc0c5
Paulsson, Mats
6b6500dc-6e7c-477b-96be-8ebdf82224bf
Wagener, Raimund
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Werner, Jörn M.
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4 February 2014
Becker, Ann-Kathrin A.
a2e4106f-21b5-4cb1-a861-2add4c906fa5
Mikolajek, Halina
c394c255-9248-4217-ace9-4a0382bfc0c5
Paulsson, Mats
6b6500dc-6e7c-477b-96be-8ebdf82224bf
Wagener, Raimund
401930b6-9833-4d2f-81d0-fc3b1ae020bd
Werner, Jörn M.
1b02513a-8310-4f4f-adac-dc2a466bd115
Becker, Ann-Kathrin A., Mikolajek, Halina, Paulsson, Mats, Wagener, Raimund and Werner, Jörn M.
(2014)
A structure of a collagen VI VWA domain displays N and C termini at opposite sides of the protein.
Structure, 22 (2), .
(doi:10.1016/j.str.2013.06.028).
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 ?3 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.
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Accepted/In Press date: 7 November 2013
e-pub ahead of print date: 12 December 2013
Published date: 4 February 2014
Organisations:
Molecular and Cellular
Identifiers
Local EPrints ID: 374192
URI: http://eprints.soton.ac.uk/id/eprint/374192
ISSN: 0969-2126
PURE UUID: ee4b0527-76a3-4136-bd2d-1bce28c3386a
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Date deposited: 09 Feb 2015 14:49
Last modified: 15 Mar 2024 03:17
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Author:
Ann-Kathrin A. Becker
Author:
Mats Paulsson
Author:
Raimund Wagener
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