Structure of the type I collagen molecule based on conformational energy computations: the triple-stranded helix and the N-terminal telopeptide.

Various studies have implicated a crucial role for the non-helical ends (telopeptides) of the collagen molecule during fibrillogenesis. In this paper, the first extensive conformational analysis of the type I collagen N-terminal telopeptide is reported. The commonly used "build-up" procedure for peptides and proteins has been used, with relevant modifications to take account of all the stereochemical constraints affecting the telopeptide. In particular, consideration was given not only to the interactions among the three chains that constitute the telopeptide, but also to the interactions between the telopeptide and the covalently linked triple helix. The computations led to a limited number of different structures within an energy range of 25 kcal/mol. Comparison of these models clearly shows that the portion of the telopeptide linked to the triple helix is rather rigid whereas its N terminus is more flexible. Furthermore, the lowest-energy structure has an energy that is markedly lower (by 7.75 kcal/mol) than that of other conformations with different structural features. The lowest-energy model of the N-terminal telopeptide, which differs from previous proposed models, has a contracted conformation compared to the triple helix region, in agreement with X-ray and neutron diffraction data on collagen fibers. Finally, the side-chains of the lysine residues of the telopeptide, involved in intermolecular cross-links in mature collagen fibers, are oriented to protrude to the exterior, in positions to interact with adjacent collagen molecules.