Abstract
Collagen is a widespread protein family involved in a variety of biological processes. The complexity of collagen and its fibrous nature prevent detailed investigations on the full‐length protein. Reductionist approaches conducted by dissecting the protein complexity through the use of model peptides have proved to be quite effective. There are, however, several issues regarding structure–stability relationships, aggregation in higher‐order assemblies, and partner recognition that are still extensively investigated. In this review, we discuss the role that side chains play in triple helix stabilization and in partner recognition. On the basis of recent literature data, we show that collagen triple helix stability is the result of the interplay of different factors. As a general trend, interactions established by amino/imino acid side chains within the triple helix scaffold effectively modulate the intrinsic residue propensity for this common structural motif. The use of peptide models has also highlighted the role that side chains play in collagen self‐association and in its interactions with receptors. Valuable examples in these fields are illustrated. Finally, future actions required to obtain more detailed information on the structure and the function of this complex protein are also delineated. Copyright © 2008 European Peptide Society and John Wiley & Sons, Ltd.