Stabilization, of the collagen triple

Bachinger, H. P., and Davis, J. M. (1991). Sequence specific thermal stability of the collagen triple-helix. Int. J. Biol. Macromol. 13, 152-156. 

Biologic Background Structure of the Collagen Triple Helix Posttranslational Modifications Stability of the Collagen Triple Helix... 

Why does hydroxylation increase the stability of the collagen triple helix ... 

Figure 3 Ring puckers of proline derivatives and their effect on the conformational stability of the collagen triple helix. The C -exo conformation corresponds to a trans (Z) orientation of the peptide bond, that native collagen helices prefer. The equilibrium ratio X trans/cis was measured by NMR in model compounds.

Prolyl 4-hydroxylation is the most abundant posttranslational modification of collagens. 4-Hydroxylation of proline residues increases the stability of the triple helix and is a key element in the folding of the collagen triple helix. " In vertebrates, almost all the Yaa position prolines of the Gly-Xaa-Yaa repeat are modified to 4(I( )-hydroxylproline by the enzyme P4H (EC 1.14.11.2), a member of Fe(II)- and 2-oxoglutarate-dependent dioxygenases. This enzyme is an 0 2/ b2-type heterotetramer in which the / subunit is PDI (EC 5.3.4.1), which is a ubiquitous disulfide bond catalyst. The P4H a subunit needs the 13 subunit for solubility however, the 13 subunit, PDI, is soluble by itself and is present in excess in the ER. Three isoforms of the a subunit have been identified and shown to combine with PDI to form [a(I)]2/ 2) [< (II)]2/32> or [a(III)]2/32 tetramers, called the type... 

Kwahara K et al (2005) Effect of hydration on the stability of the collagen-like triple-helical structure of [4(R)-hydroxyprolyl-4(R)-hydroxyprolylglycine.io. Biochem 44 15812-15822 PDBID 1WZB... 

Bachinger HP, Morris NP, Davis JM Thermal stability and folding of the collagen triple helix and the effects of mutations in osteogenesis imperfecta on the triple helix of type I collagen., 1/ / J Med Genet 45 152-162,1993. 

In the context of the collagen triple helix it can be concluded that the Cf-exo pucker of the proline in Yaa position is favored by stereoelectronic effects of a (4R)-OH substituent which also stabilizes the traus-Xaa-(4R)-Hyp peptide bond, thus preorganizing this residue in a conformation that best befits a triple helix. Conversely, in the Xaa position the Pro residue is preferred in the Cy-endo pucker the related dihedral angles are reported in Table 11.3. 

Engel, J. and Bachinger, H. P. (2005). Structure, stability and folding of the collagen triple heUx. In "Collagen Primer in Structure, Processing and Assembly", (J. Brinckmann,... 

It is well known that native collagen containes tripeptide sequences, which alone are not capable of building up a triple helix (e.g. Gly-Pro-Leu, Gly-Pro-Ser) when they exist as homopolypeptides. The synthesis of threefold covalently bridged peptide chains opens up the possibility of investigating the folding properties of such weak helix formers, because the bridging reduces the entropy loss during triple-helix formation and thereby increases the thermodynamic stability of the tertiary structure. Therefore, we have... 

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