The irreplaceable glycine: glycine homologs destabilize the collagen triple helix

Collagen, the most widespread protein in animals, contains glycine as every third amino acid. This regular repetition of glycine residues is required for the tight packing of the collagen triple helix. In this work, we substitute glycine with its homolog β-alanine in collagen model peptides (CMPs) and study the effect of β-alanine on the formation of triple helices. While β-alanine in the middle of CMP sequences is incompatible with triple helix formation, terminal β-alanine residues are tolerated. The work highlights the critical role of glycine in collagen.