Heterogeneity of Collagen VI Microfibrils: STRUCTURAL ANALYSIS OF NON-COLLAGENOUS REGIONS.
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 small angle x-ray scattering (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.
['Maaß|Tobias|T|', 'Bayley|Christopher P|CP|', 'Mörgelin|Matthias|M|', 'Lettmann|Sandra|S|', 'Bonaldo|Paolo|P|', 'Paulsson|Mats|M|', 'Baldock|Clair|C|', 'Wagener|Raimund|R|']
D000595:Amino Acid Sequence D000818:Animals D024141:Collagen Type IV D057809:HEK293 Cells D006801:Humans D051379:Mice D008969:Molecular Sequence Data D017510:Protein Folding D055503:Protein Multimerization D017434:Protein Structure, Tertiary
collagen microfibrils VWA domain electron microscopy (EM) extracellular matrix single particle analysis small-angle x-ray scattering (SAXS)