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 alpha1(VI), alpha2(VI), and alpha3(VI) chains, the formation of dimers is determined principally by interactions of the alpha2(VI) chain. Key components of this interaction are the metal ion-dependent adhesion site (MIDAS) motif of the alpha2C2 A-domain and the GER sequence in the helical domain of another alpha2(VI) chain. Replacement of the alpha2(VI) C2 domain with the alpha3(VI) domain abolished dimer formation, whereas alterations in the alpha2(VI) C1 domain did not disrupt dimer formation. When the helical sequences were investigated, replacement of the alpha2(VI) sequence GSPGERGDQ with the alpha3(VI) sequence GEKGERGDV abolished dimer formation. Mutating the Pro-108 to a Lys-108 in this alpha2(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 alpha2(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.
Highlights
Type VI collagen has a ubiquitous distribution throughout connective tissues, and it is thought to link cells and other matrix components
These results demonstrate that the ␣2(VI) chain position in the assembled triple-helical molecule is critical for antiparallel dimer formation and identify the interacting collagenous and metal ion-dependent adhesion site (MIDAS) sequences involved
Side chains from three loops closely opposed on the upper surface of the domain coordinate a Mg2ϩ or Mn2ϩ ion, to form a three-dimensional metal ion-dependent adhesion site (MIDAS),1 which is conserved in all ␣I-domains
Summary
Despite the fact that type VI collagen is a heterotrimer composed of ␣1(VI), ␣2(VI), and ␣3(VI) chains, the formation of dimers is determined principally by interactions of the ␣2(VI) chain Key components of this interaction are the metal ion-dependent adhesion site (MIDAS) motif of the ␣2C2 A-domain and the GER sequence in the helical domain of another ␣2(VI) chain. Mutating the Pro-108 to a Lys-108 in this ␣2(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 ␣2(VI) chain position in the assembled triple-helical molecule is critical for antiparallel dimer formation and identify the interacting collagenous and MIDAS sequences involved. We have investigated the role of the ␣2C2 MIDAS site in dimer formation to define the molecular recognition sequences that determine intracellular type VI collagen assembly
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