title: Collagen VI, conformation of A-domain arrays and microfibril architecture.
abstract: Collagen VI is a ubiquitous extracellular matrix protein that assembles into beaded microfibrils that form networks linking cells to the matrix. Collagen VI microfibrils are typically formed from a heterotrimer of the α1, α2, and α3 chains. The α3 chain is distinct as it contains an extended N terminus with up to 10 consecutive von Willebrand factor type A-domains (VWA). Here, we use solution small angle x-ray scattering (SAXS) and single particle analysis EM to determine the nanostructure of nine of these contiguous A-domains. Both techniques reveal a tight C-shape conformation for the A-domains. Furthermore, using biophysical approaches, we demonstrate that the N-terminal region undergoes a conformational change and a proportion forms dimers in the presence of Zn(2+). This is the first indication that divalent cations interact with collagen VI A-domains. A three-dimensional reconstruction of tissue-purified collagen VI microfibrils was generated using EM and single particle image analysis. The reconstruction showed the intricate architecture of the collagen VI globular regions, in particular the highly structurally conserved C-terminal region and variations in the appearance of the N-terminal region. The N-terminal domains project out from the globular beaded region like angled radial spokes. These could potentially provide interactive surfaces for other cell matrix molecules.
authors: Wellcome Trust Centre for Cell-Matrix Research, University of Manchester, Manchester M13 9PT, United Kingdom.
authors: Nicola
authors: N
authors: Beecher
authors: Alan M
authors: AM
authors: Roseman
authors: Thomas A
authors: TA
authors: Jowitt
authors: Richard
authors: R
authors: Berry
authors: Helen
authors: H
authors: Troilo
authors: Richard A
authors: RA
authors: Kammerer
authors: C Adrian
authors: CA
authors: Shuttleworth
authors: Cay M
authors: CM
authors: Kielty
authors: Clair
authors: C
authors: Baldock
mesh_terms: D024142:Collagen Type VI / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D020894:Microfibrils / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D055503:Protein Multimerization / Q000502:physiology*; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary
chemical_list: D024142:Collagen Type VI