Type I collagen N-telopeptides adopt an ordered structure when docked to their helix receptor during fibrillogenesis

The in vitro rate and specificity of fibrillogenesis in type I collagen depends on the integrity of the amino (N)-telopeptide domain. In vivo an intact N-telopeptide domain is also required for normal fibril assembly. Although Chou-Fasman predictions and NMR studies suggested that a type I beta-turn could be induced in alpha1(I) N-telopeptide chains, computer modeling did not identify ordered structures. Nevertheless, X-ray analysis and electron tomography studies have shown that the N-telopeptide is in one of the most highly ordered fibril domains. This study was undertaken to determine if the docking of the N-telopeptide to its helix receptor domain could induce the telopeptides to take up a specific conformation. With use of molecular modeling suite of programs, a (Gly-Pro-Pro)(n) triple-helical structure was built on the basis of high-resolution X-ray crystallographic coordinates and then replaced with the actual bovine collagen residues 924-938, the triple-helical alpha1(I)-N-telopeptide-receptor sequences. Energy minimization produced a modified triple-helical conformation. The bovine alpha1(I) N-telopeptide sequence was similarly minimized and docked to this receptor. The docking induced an ordered conformation with a stabilizing hydrogen bond in the N-telopeptide and, importantly, a reciprocal reordering of the triple-helical conformation in the binding domain. This docked structure placed Lys residues in both telopeptide and helix in the correct locations for cross-link formation. The modeling has been extended to the three-chain N-telopeptide domain and finally to the construction of the Hulmes-Miller quasi-hexagonal packing structure. Each N-telopeptide domain can form linkages with two adjacent, aligned helix receptor domains. The telopeptides and the order of staggering of the three chains in the helix play crucial roles in the packing and intrafibrillar cross-linking patterns and the relative azimuthal orientations of adjacent molecules in the fibril. The models confirm the high order in the N-telopeptide 4D overlap zone.