9DP0

Fibrillar assembly of racemic, C-alpha methylated, macrocyclic beta-hairpins

これはPDB形式変換不可エントリーです。

9DP0 の概要

• エントリーDOI: 10.2210/pdb9dp0/pdb
• 関連するPDBエントリー: 2N1E
• 分子名称: racemic, C-alpha methylated, macrocyclic beta-hairpin, CITRATE ANION, PENTAETHYLENE GLYCOL, ... (4 entities in total)
• 機能のキーワード: max1, fibril, hydrogel, c-alpha methylated macrocyclic beta-hairpin, protein fibril
• 由来する生物種: synthetic construct
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 6242.96

構造登録者

Samdin, T.D.,Lubkowski, J.,Anderson, C.F.,Schneider, J.P. (登録日: 2024-09-20, 公開日: 2025-04-30, 最終更新日: 2025-05-07)

主引用文献

Samdin, T.D.,Lubkowski, J.,Anderson, C.F.,Schneider, J.P.
From Hydrogel to Crystal: A Molecular Design Strategy that Chemically Modifies Racemic Gel-Forming Peptides to Furnish Crystalline Fibrils Stabilized by Parallel Rippled beta-Sheets.
J.Am.Chem.Soc., 147:14377-14387, 2025

PubMed Abstract: Rippled β-sheets are an underutilized secondary structural motif that hold promise in the rational design of peptide hydrogel materials with unique and desirable properties. Fully capitalizing on the design potential of this structural element, however, requires a high-resolution molecular understanding of the interactions they form within the supramolecular assemblies comprising the material - which are absent in all reports to date. Herein, we develop a molecular design strategy to modulate the phase state of β-hairpin peptides prone to form fibrillar gels into ones that assemble into crystal lattices, making high-resolution structural analysis possible. Truncating, cyclizing and Cα-methylating enantiomeric gel-forming peptides affords mirror-image macrocyclic peptides. Crystallography reveals that the enantiomeric macrocycles coassemble to form racemic fibril-like assemblies of unprecedented structure. Extended arrays of sheet-rich fibrils contain alternating blocks of enantiopure β-hairpins that assemble to form both canonical pleated β-sheets as well as stereocomplexed rippled β-sheets. This structure illuminates new molecular interactions to leverage in the design of next generation peptide hydrogels and provides the first crystallographic evidence of a parallel rippled β-sheet.

PubMed: 40252045
DOI: 10.1021/jacs.5c00671

実験手法

X-RAY DIFFRACTION (2 Å)