2RQ8

Solution NMR structure of titin I27 domain mutant

2RQ8 の概要

• エントリーDOI: 10.2210/pdb2rq8/pdb
• 関連するPDBエントリー: 1TIT
• 分子名称: Titin (1 entity in total)
• 機能のキーワード: beta-sandwich, immunoglobulin-like domain, alternative splicing, atp-binding, calcium, calmodulin-binding, cardiomyopathy, coiled coil, cytoplasm, disease mutation, disulfide bond, immunoglobulin domain, isopeptide bond, kelch repeat, kinase, limb-girdle muscular dystrophy, magnesium, metal-binding, nucleotide-binding, nucleus, phosphoprotein, polymorphism, serine/threonine-protein kinase, tpr repeat, transferase, ubl conjugation, wd repeat
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Cytoplasm (Probable): Q8WZ42
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 10930.48

構造登録者

Yagawa, K.,Oguro, T.,Momose, T.,Kawano, S.,Sato, T.,Endo, T. (登録日: 2009-03-05, 公開日: 2010-02-02, 最終更新日: 2024-05-29)

主引用文献

Yagawa, K.,Yamano, K.,Oguro, T.,Maeda, M.,Sato, T.,Momose, T.,Kawano, S.,Endo, T.
Structural basis for unfolding pathway-dependent stability of proteins: Vectorial unfolding vs. global unfolding
Protein Sci., 2010

PubMed Abstract: Point mutations in proteins can have different effects on protein stability depending on the mechanism of unfolding. In the most interesting case of I27, the Ig-like module of the muscle protein titin, one point mutation (Y9P) yields opposite effects on protein stability during denaturant-induced "global unfolding" versus "vectorial unfolding" by mechanical pulling force or cellular unfolding systems. Here, we assessed the reason for the different effects of the Y9P mutation of I27 on the overall molecular stability and N-terminal unraveling by NMR. We found that the Y9P mutation causes a conformational change that is transmitted through beta-sheet structures to reach the central hydrophobic core in the interior and alters its accessibility to bulk solvent, which leads to destabilization of the hydrophobic core. On the other hand, the Y9P mutation causes a bend in the backbone structure, which leads to the formation of a more stable N-terminal structure probably through enhanced hydrophobic interactions.

PubMed: 20095049
DOI: 10.1002/pro.346

実験手法

SOLUTION NMR