Abstract
Cation-π interactions are found to be an important noncovalent force in proteins. Collagen is a right-handed triple helix composed of three left-handed PPII helices, in which (X-Y-Gly) repeats dominate in the sequence. Molecular modeling indicates that cation-π interactions could be formed between the X and Y positions in adjacent collagen strands. Here, we used a host-guest peptide system: (Pro-Hyp-Gly) 3 -(Pro-Y-Gly-X-Hyp-Gly)-(Pro-Hyp-Gly) 3 , where X is an aromatic residue and Y is a cationic residue, to study the cation-π interaction in the collagen triple helix. Circular dichroism (CD) measurements and T m data analysis show that the cation-π interactions involving Arg have a larger contribution to the conformational stability than do those involving Lys, and Trp forms a weaker cation-π interaction with cationic residues than expected as a result of steric effects. The results also show that the formation of cation-π interactions between Arg and Phe depends on their relative positions in the strand. Moreover, the fluorinated and methylated Phe substitutions show that an electron-withdrawing or electron-donating substituent on the aromatic ring can modulate its π-electron density and the cation-π interaction in collagen. Our data demonstrate that the cation-π interaction could play an important role in stabilizing the collagen triple helix. © 2010 Elsevier Inc. All rights reserved.