Preferred proline puckerings in cis and trans peptide groups: Implicationsfor collagen stability

The interplay between side-chain and main-chain conformations is a distinct ive characteristic of proline residues. Here we report the results of a sta tistical analysis of proline conformations using a large protein database. In particular, we found that proline residues with the preceding peptide, b ond in the cis state preferentially adopt a down puckering. Indeed, out of 178 cis proline residues, as many as 145 (81%) are down. By analyzing the 1 -4 and 1-5 nonbonding distances between backbone atoms, we provide a struct ural explanation for the observed trend. The observed correlation between p roline puckering and peptide bond conformation suggests a new mechanism to explain the reported shift of the cis-trans equilibrium in proline derivati ves. The implications of these results for the current models of collagen s tability are also discussed.