Molecular Mechanism for the Phylogenetic Change of Thermostability of Fibril-Forming Collagen. Evidence that (Gly-X-Hyp) Triplets are Main Factors Determining Stability of Collagen

Published data relating the concentration of 4-hydroxyproline residues to the stability of collagen was used to estimate the different effects of two types of triplets: (Gly-X-Hyp) and (Gly-Pro-Hyp). The data comprised mainly fibril-forming collagens, which exhibit highly cooperative helix-coil transitions at temperatures that are remarkably close to body temperature. A wide range of denaturation temperatures was therefore ensured by including collagen from different species of fish, including some living in the arctic, amphibians and mammals. As a first approximation, the dependence of the denaturation temperature, Td, of collagen on hydroxyproline content was considered as a linear function: Td = T0 + K1N(GXO) + K2N(GPO), where the coefficients K1 and K2 characterize the degree of influence of the two types of triplet. Regression analyses showed that K1 exceeded K2 by about 10 times. Analysis of the dependence of the enthalpy of denaturation on hydroxyproline content also showed that triplets of the type (Gly-X-Hyp) containing water had a larger effect than (Gly-Pro-Hyp) triplets and that the primary factor determining increased stability was the concentration of (Gly-XHyp) triplets, while (Gly-Pro-Hyp) triplets governed the nonlinear character of the relationship. We conclude that the main factor stabilizing the collagen triple helix and governing the phylogenetic change of collagen thermostability is the concentration of triplets of the type (Gly-X-Hyp). © 2010 Bull. Georg. Natl. Acad. Sci.