Structure, Stability and Folding of the Collagen Triple Helix

Abstract

The collagen triple helix is a widespread structural element, which not only occurs in collagens but also in many other proteins. The triple helix consists of three identical or different polypeptide chains with the absolute requirement of a -Gly-Xaa-Yaa- repeat, in which the amino acid residues in X- and Y-position are frequently proline or hydroxyproline. The freezing of φ-angles in polypeptide backbone by proline rings and other steric restrictions are essential for stabilization. The OH-group of 4(R)-hydroxyproline, normally located in the Y-position, has an additional stabilizing effect. On the other hand, peptide bonds preceding proline and hydroxyproline are up to 20% in cis-configuration in unfolded chains and the need for a relatively slow cis-trans isomerization provides kinetic difficulties in triple helix formation. Because of their repeating structure, collagen chains easily misalign during folding. Therefore, oligomerization domains flank triple helical domains in natural collagens. The mechanism by which these domains influence stability and kinetics was elucidated with model peptides using different types of trimerization domains. Finally, the review briefly describes mutations in collagen triple helices, which cause severe inherited diseases by disturbances of folding.