Peptide bonds revisited

For many years it has been almost dogma in the scientific community that in protein structures the planar peptide bond occurs predominantly in the trans conformation1. The occasional occurrence of a peptide bond in cis conformation was, in most cases, noted as a curiosity of the respective structure. This is remarkable since it became clear almost 20 years ago that the cis/trans-isomerization of peptide bonds on the N-terminal side of proline plays an important role in the folding process of a protein2. Systematic studies of peptide bond conformations have been hampered by the limited amount of structural information available3, and have so far mainly focused on proline residues4. With more three-dimensional structures of proteins at hand today, the notion is slowly emerging that cis peptide bonds are by no means a curiosity, and that they may even be important determinants for the function of proteins.