Heterotrimeric type I collagen C-telopeptide conformation as docked to its helix receptor.
The amino (N-telo) and carboxyl (C-telo) telopeptides of type I collagen play crucial roles, in vivo and in vitro, in the assembly of collagen fibrils, regulating the axial alignment of the molecules within a fibril, azimuthal orientations of neighboring molecules, and cross-link formation. High-resolution structures of the telopeptides are not available from X-ray diffraction studies, but computational methods permitted prediction of the N-telo structure within a fibril. Here, using a suite of molecular modeling software, the more complex heterotrimeric C-telo of human type I collagen has been built from the correct sequences and energy minimized and the energy minimum confirmed by molecular dynamics. The receptor triple helix was modeled on the basis of the Protein Data Bank coordinates of a collagen-like sequence. Docking of the heterotrimeric C-telopeptide to its receptor showed that hydrophobic interactions involving the short alpha2 C-telopeptide are crucial determinants of its azimuthal orientation within the docked structure. A docked C-telo can interact with only one neighboring helix. The two alpha1(I) C-telo chains in the alpha1(Alpha)-alpha2-alpha1(B) chain stagger do not have identical docked conformations, and one of the alpha1(I) C-telo chains appears to be favored for formation of a cross-link between its K(16C) and a helix K87. Prior studies showed that a docked N-telopeptide can interact with two adjacent collagen monomers, forming a tightly packed region. A recent X-ray analysis showed the N- and C-telo regions pack differently, with the C-telo region being less densely packed than N-telo regions. This difference between N- and C-telopeptide docked structures demonstrates how unique and specific packing can occur in the fibril at each boundary of the type I collagen gap region.