7JX4

Crystal Structure of N-Lysine Peptoid-modified Collagen Triple Helix

7JX4 の概要

• エントリーDOI: 10.2210/pdb7jx4/pdb
• 関連するPDBエントリー: 6w47
• 分子名称: Collagen mimetic peptide with N-Lysine guest (2 entities in total)
• 機能のキーワード: collagen, peptoid, triple helix, hyper-stable, protein fibril
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 5832.26

構造登録者

Yu, M.S.,Whitby, F.G.,Hill, C.P.,Kessler, J.L.,Yang, L.D. (登録日: 2020-08-26, 公開日: 2021-07-21, 最終更新日: 2023-11-15)

主引用文献

Kessler, J.L.,Kang, G.,Qin, Z.,Kang, H.,Whitby, F.G.,Cheatham, T.E.,Hill, C.P.,Li, Y.,Yu, S.M.
Peptoid Residues Make Diverse, Hyperstable Collagen Triple-Helices.
J.Am.Chem.Soc., 143:10910-10919, 2021

PubMed Abstract: As the only ribosomally encoded N-substituted amino acid, proline promotes distinct secondary protein structures. The high proline content in collagen, the most abundant protein in the human body, is crucial to forming its hallmark structure: the triple-helix. For over five decades, proline has been considered compulsory for synthetic designs aimed at recapitulating collagen's structure and properties. Here we describe that N-substituted glycines (N-glys), also known as peptoid residues, exhibit a general triple-helical propensity similar to or greater than proline, enabling synthesis of stable triple-helical collagen mimetic peptides (CMPs) with unprecedented side chain diversity. Supported by atomic-resolution crystal structures as well as circular dichroism and computational characterizations spanning over 30 N-gly-containing CMPs, we discovered that N-glys stabilize the triple-helix primarily by sterically preorganizing individual chains into the polyproline-II helix. We demonstrated that N-glys with exotic side chains including a "click"-able alkyne and a photosensitive side chain enable CMPs for functional applications including the spatiotemporal control of cell adhesion and migration. The structural principles uncovered in this study open up opportunities for a new generation of collagen-mimetic therapeutics and materials.

PubMed: 34255504
DOI: 10.1021/jacs.1c00708

実験手法

X-RAY DIFFRACTION (0.95 Å)