Cation-π Interaction Induced Folding of AAB-Type Collagen Heterotrimers.

Collagen is the most predominant component of the extracellular matrix. Natural collagens consist of all identical (AAA, homotrimer), two different (AAB, heterotrimer), or three different (ABC, heterotrimer) peptide chains. Many natural collagens are either AAB- or ABC-type heterotrimers, making heterotrimeric helices better mimics for studying collagen structures in nature. We prepared collagen-mimetic peptides containing cationic (Arg) or aromatic (Phe, Tyr) residues to explore collagen heterotrimer folding via cation-π interactions. Circular dichroism, differential scanning calorimetry, and nuclear magnetic resonance (NMR) measurements showed that the interchain cation-π interactions between cationic and aromatic peptides could induce AAB-type heterotrimer formation. By controlling the mixing molar ratios of cationic and aromatic peptides in solution, we could obtain the heterotrimers with various compositions. We demonstrate the effectiveness of cation-π interactions as a force to fold collagen heterotrimers.