Contributions of cation-π interactions to the collagen triple helix stability.
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 Tm 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.
Department of Chemistry, National Tsing Hua University, Hsinchu 30013, Taiwan, ROC.
Chia-Ching
CC
Chen
Wei
W
Hsu
Kuo-Chu
KC
Hwang
Jih Ru
JR
Hwu
Chun-Cheng
CC
Lin
Jia-Cherng
JC
Horng
D000595:Amino Acid Sequence; D024322:Amino Acids, Aromatic / Q000737:chemistry / Q000378:metabolism; D002412:Cations / Q000737:chemistry / Q000378:metabolism; D003094:Collagen / Q000737:chemistry* / Q000378:metabolism; D004579:Electron Transport; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D055550:Protein Stability; D017433:Protein Structure, Secondary
D024322:Amino Acids, Aromatic; D002412:Cations; D010446:Peptide Fragments; D003094:Collagen