Modulating the Stability of Collagen Triple Helices by Terminal Charged Residues.

Abstract

Cationic or anionic residues are frequently located at the termini of proteins because their charged side chain can form electrostatic interactions with a terminal carboxylate or ammonium group to stabilize the structure under physiological conditions. Here, we used collagen-mimetic peptides (CMPs) to examine how the terminal charge-charge interactions affect the collagen triple helix stability. We designed a series of CMPs with either a Lys or Glu incorporated into the terminus and measured their pH-dependent stability. The results showed that the terminal electrostatic attractions stabilized the triple helix, while the terminal electrostatic repulsions destabilized the trimer. The data also revealed that the repulsions imposed a greater effect than did the attractions on the triple helix. An amino acid with a shorter side chain, such as aspartate and ornithine, was also installed to investigate the length effect on electrostatic interactions, which was found to be insignificant. Meanwhile, simultaneously incorporating cationic and anionic residues into the termini showed slight additive stabilization effects but pronounced additive destabilization consequences. We have demonstrated that the collagen triple helix stability can be modulated by introducing a cationic or anionic residue into the terminus of a peptide, giving useful information for the design of collagen-associated materials.