2RJY

Crystal structure of villin headpiece, P21 21 21 space group

2RJY の概要

• エントリーDOI: 10.2210/pdb2rjy/pdb
• 関連するPDBエントリー: 1YU8 1yu5 1yu7 2RJV 2RJW 2RJX 2RJY
• 分子名称: Villin-1 (2 entities in total)
• 機能のキーワード: helix, actin capping, actin-binding, calcium, cytoplasm, cytoskeleton, structural protein
• 由来する生物種: Gallus gallus (Chicken)
• 細胞内の位置: Cytoplasm, cytoskeleton: P02640
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 7611.66

構造登録者

Meng, J.,McKnight, C.J. (登録日: 2007-10-16, 公開日: 2008-09-23, 最終更新日: 2023-08-30)

主引用文献

Meng, J.,McKnight, C.J.
Crystal structure of a pH-stabilized mutant of villin headpiece.
Biochemistry, 47:4644-4650, 2008

PubMed Abstract: Villin-type headpiece domains are compact F-actin-binding motifs that have been used extensively as a model system to investigate protein folding by both experimental and computational methods. Villin headpiece (HP67) harbors a highly helical, thermostable, and autonomously folding subdomain in the C terminus (HP35), and because of this feature, HP67 is usually considered to be composed of a N- and C-terminal subdomain. Unlike the C-terminal subdomain, the N-terminal subdomain consists mainly of loops and turns, and the folding is dependent upon the presence of the C-terminal subdomain. The pH sensitivity of this subdomain is thought to arise from, at least partially, protonation of H41 buried in the hydrophobic core. Substitution of this histidine with tyrosine, another permissive residue at this position for naturally occurring sequences, increases not only the pH stability of HP67 but also the thermal stability and the cooperativity of thermal unfolding over a wide pH range (0.9-7.5). The crystal structures of wild-type HP67 and the H41Y mutant, determined under the same conditions, indicate that the H41Y substitution causes only localized rearrangement around the mutated residue. The F-actin-binding motif remains essentially the same after the mutation, accounting for the negligible effect of the mutation on F-actin affinity. The hydrogen bond formed between the imidazole ring of H41 and the backbone carbonyl of E14 of HP67 is eliminated by the H41Y mutation, which renders the extreme N terminus of H41Y more mobile; the hydrogen bond formed between the imidazole ring of H41 and the backbone nitrogen of D34 is replaced with that between the hydroxyl group of Y41 and the backbone nitrogen of D34 after the H41Y substitution. The increased hydrophobicity of tyrosine compensates for the loss of hydrogen bonds in the extreme N terminus and accounts for the increased stability and cooperativity of the H41Y mutant.

PubMed: 18370407
DOI: 10.1021/bi7022738

実験手法

X-RAY DIFFRACTION (1.4 Å)