Amino acid propensities for the collagen triple-helix

Determination of the tendencies of amino acids to form alpha -helical and b eta -sheet structures has been important in clarifying stabilizing interact ions, protein design, and the protein folding problem. In this study, we ha ve determined for the first time a complete scale of amino acid propensitie s for another important protein motif: the collagen triple-helix conformati on with its Gly-X-Y repeating sequence. Guest triplets of the form Gly-X-Hy p and Gly-Pro-Y are used to quantitate the conformational propensities of a ll 20 amino acids for the X and Y positions in the context of a (Gly-Pro-Hy p)(8) host peptide. The rankings for both the X and Y positions show the hi ghly stabilizing nature of imino acids and the destabilizing effects of Gly and aromatic residues. Many residues show differing propensities in the X versus Y position, related to the nonequivalence of these positions in term s of interchain interactions and solvent exposure. The propensity of amino acids to adopt a polyproline II-like conformation plays a role in their tri ple-helix rankings, as shown by a moderate correlation of triple-helix prop ensity with frequency of occurrence in polyproline II-like regions. The hig h propensity of ionizable residues in the X position suggests the importanc e of interchain hydrogen bonding directly or through water to backbone carb onyls or hydroxyprolines. The low propensity of side chains with branching at the C-delta in the Y position supports models suggesting these groups bl ock solvent access to backbone C=O groups. These data provide a first step in defining sequence-dependent variations in local triple-helix stability a nd binding, and are important for a general understanding of side chain int eractions in all proteins.