Structural basis of type VI collagen dimer formation.

Abstract We have determined the interactive sites required for dimer formation in type VI collagen. Despite the fact that type VI collagen is a heterotrimer composed of α1(VI), α2(VI), and α3(VI) chains, the formation of dimers is determined principally by interactions of the α2(VI) chain. Key components of this interaction are the metal ion-dependent adhesion site (MIDAS) motif of the α2C2 A-domain and the GER sequence in the helical domain of another α2(VI) chain. Replacement of the α2(VI) C2 domain with the α3(VI) domain abolished dimer formation, whereas alterations in the α2(VI) C1 domain did not disrupt dimer formation. When the helical sequences were investigated, replacement of the α2(VI) sequence GSPGERGDQ with the α3(VI) sequence GEKGERGDV abolished dimer formation. Mutating the Pro-108 to a Lys-108 in this α2(VI) sequence did not influence dimer formation and suggests that, unlike the integrin I-domain/triple-helix interaction, hydroxyproline is not required in collagen VI A-domain/helix interaction. These results demonstrate that the α2(VI) chain position in the assembled triple-helical molecule is critical for antiparallel dimer formation and identify the interacting collagenous and MIDAS sequences involved. These interactions underpin the subsequent assembly of type VI collagen.