Cation−π Interactions and Their Role in Assembling Collagen Triple Helices

Abstract

Cation−π interactions play a significant role in the stabilization of globular proteins. However, their role in collagen triple helices is less well understood and they have rarely been used in de novo designed collagen mimetic systems. In this study, we analyze the stabilizing and destabilizing effects in pairwise amino acid interactions between cationic and aromatic residues in both axial and lateral sequential relationships. Thermal unfolding experiments demonstrated that only axial pairs are stabilizing, while the lateral pairs are uniformly destabilizing. Molecular dynamics simulations show that pairs with an axial relationship can achieve a near-ideal interaction distance, but pairs in a lateral relationship do not. Arginine−π systems were found to be more stabilizing than lysine−π and histidine−π. Arginine−π interactions were then studied in more chemically diverse ABCtype heterotrimeric helices, where arginine−tyrosine pairs were found to form the best helix. This work helps elucidate the role of cation−π interactions in triple helices and illustrates their utility in designing collagen mimetic peptides.

Heterotrimeric collagen peptides: design, characterization, and applications

“…Hartgerink等 [47] 设计了多肽C R 、A F 、A Y 以及A W , 图 4 静电相互作用形成异源三聚体. (a) 异源三聚体 (DOG) 10 •(PKG) 10 •(POG) 10 的分子模型 [38] ; (b) 静电相互作用 介导下形成的AAB型异源三聚体 [39] ; (c) O和P分别被K和D 选择性替换的胶原多肽在静电相互作用介导下形成稳定的 ABC型异源三聚体 [41] ; (d) 不含有氨基酸O的胶原多肽 (PKG) 10 、(EPG) 10 和(DKG) 10 形成的异源三聚体 [42] (网络版 彩图) 图 5 通过计算优化构建的静电相互作用介导形成的异源 三聚体 [43] .…”

Stabilization of Synthetic Collagen Triple Helices: Charge Pairs and Covalent Capture

“…Of the pairwise interactions, charge pairs between the cationic amino acids lysine (K) and arginine (R) and the anionic aspartate (D) and glutamate (E) have been studied in the greatest detail. By utilizing these charge pairs, control of assembly of biomimetic collagen heterotrimers has been achieved. − It has been found that in a triple helix, the pairwise charge pairs are presented in two distinct geometries, axial and lateral. ,− For example, a lysine–aspartate interaction in the axial geometry results in a large thermal stabilization, but a lateral geometry confirms little to no stabilization.…”

Collagen Mimicry with a Short Collagen Model Peptide

“…[2] The controllable design, tuneable properties, and biocompatibility of CMPs have garnered significant interest in the fields of tissue engineering, drug delivery, and regenerative medicine. [12,13] While numerous CMP sequences capable of forming a triple helix have been reported over the years, [14][15][16][17][18][19][20][21][22] only a limited number of sequences have demonstrated predominant self-assembly into a network of fibrils. [16,23] A large number of CMP peptide sequences form nonordered aggregates which is undesirable where applications necessitate the predominance of fibrils.…”