Heterogeneity of Collagen VI Microfibrils: Structural Analysis of Non-collagenous Regions.

Research output: Contribution to journalArticle

Abstract

Collagen VI, a collagen with uncharacteristically large N- and C-terminal non-collagenous regions, forms a distinct microfibrillar network in most connective tissues. It was long considered to consist of three genetically distinct α chains (α1, α2 and α3). Intracellularly heterotrimeric molecules associate to form dimers and tetramers, which are then secreted and assembled to microfibrils. The identification of three novel long collagen VI α chains α4, α5, and α6 led to the question if and how these may substitute for the long α3 chain in collagen VI assembly. Here we studied structural features of the novel long chains, and analyzed the assembly of these into tetramers and microfibrils. N- and C-terminal globular regions of collagen VI were recombinantly expressed and studied by SAXS. Ab initio models of the N-terminal globular regions of the α4, α5 and α6 chains showed a C-shaped structure similar to that found for the α3 chain. Single particle EM nanostructure of the N-terminal globular region of the α4 chain confirmed the C-shaped structure revealed by SAXS. Immuno EM of collagen VI extracted from tissue revealed that like the α3 chain the novel long chains assemble to homotetramers that are incorporated into mixed microfibrils. Moreover, SAXS models of the C-terminal globular regions of the α1, α2, α4, and α6 chains were generated. Interestingly, the α1, α2 and α4 C-terminal globular regions dimerize. These self-interactions may play a role in tetramer formation.

Details

Authors
  • Tobias Maaß
  • Christopher P Bayley
  • Matthias Mörgelin
  • Sandra Lettmann
  • Paolo Bonaldo
  • Mats Paulsson
  • Clair Baldock
  • Raimund Wagener
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cell and Molecular Biology
Original languageEnglish
Pages (from-to)5247-5258
JournalJournal of Biological Chemistry
Volume291
Issue number10
Early online date2016 Jan 7
Publication statusPublished - 2016
Publication categoryResearch
Peer-reviewedYes