9YM2

Backbone Modification in the Villin Headpiece Miniprotein: HP35 with ACPC at Position 29

9YM2 の概要

• エントリーDOI: 10.2210/pdb9ym2/pdb
• NMR情報: BMRB: 31273
• 分子名称: Villin-1 (1 entity in total)
• 機能のキーワード: miniprotein, heterogeneous backbone, proteomimetic, structural protein
• 由来する生物種: Gallus gallus (chicken)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 4026.64

構造登録者

Lin, Y.,David, R.M.,Amin, D.M.,Osborne, S.W.J.,Horne, W.S. (登録日: 2025-10-09, 公開日: 2026-01-07)

主引用文献

Lin, Y.,David, R.M.,Amin, D.M.,Osborne, S.W.J.,Horne, W.S.
Backbone engineering in the hydrophobic core of villin headpiece.
Rsc Chem Biol, 2025

PubMed Abstract: Changing the backbone connectivity of proteins can impart useful new traits while maintaining essential structural and functional features. In design of artificial proteomimetic agents, backbone modification is usually isolated to sites that are solvent-exposed in the folded state, as similar changes at buried residues can alter the fold. Recent work has shown that core backbone modification without structural perturbation is possible; however, the modifications in that study were consistently destabilizing and made in a prototype of exceptionally high conformational stability. Here, we report efforts to broaden the scope and improve the efficacy of core backbone engineering by applying it to the C-terminal subdomain of villin headpiece. A series of variants are prepared in which different artificial residue types are incorporated at core positions throughout the sequence, including a crucial aromatic triad. Impacts on folding energetics are quantified by biophysical methods, and high-resolution structures of several variants determined by NMR. We go on to construct a variant with ∼40% of its core modified that adopts a fold identical to the prototype while showing enhanced thermodynamic stability.

PubMed: 41450753
DOI: 10.1039/d5cb00269a

実験手法

SOLUTION NMR