2LP5

Native Structure of the Fyn SH3 A39V/N53P/V55L

2LP5 の概要

• エントリーDOI: 10.2210/pdb2lp5/pdb
• 関連するPDBエントリー: 1SHF 2L2P 3CQT
• NMR情報: BMRB: 17149
• 分子名称: Tyrosine-protein kinase Fyn (1 entity in total)
• 機能のキーワード: amyloid fibril, protein folding intermediate, transferase
• 由来する生物種: Gallus gallus (bantam,chickens)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 7538.24

構造登録者

Neudecker, P.,Robustelli, P.,Cavalli, A.,Vendruscolo, M.,Kay, L.E. (登録日: 2012-02-06, 公開日: 2012-05-16, 最終更新日: 2024-05-15)

主引用文献

Neudecker, P.,Robustelli, P.,Cavalli, A.,Walsh, P.,Lundstrom, P.,Zarrine-Afsar, A.,Sharpe, S.,Vendruscolo, M.,Kay, L.E.
Structure of an intermediate state in protein folding and aggregation.
Science, 336:362-366, 2012

PubMed Abstract: Protein-folding intermediates have been implicated in amyloid fibril formation involved in neurodegenerative disorders. However, the structural mechanisms by which intermediates initiate fibrillar aggregation have remained largely elusive. To gain insight, we used relaxation dispersion nuclear magnetic resonance spectroscopy to determine the structure of a low-populated, on-pathway folding intermediate of the A39V/N53P/V55L (A, Ala; V, Val; N, Asn; P, Pro; L, Leu) Fyn SH3 domain. The carboxyl terminus remains disordered in this intermediate, thereby exposing the aggregation-prone amino-terminal β strand. Accordingly, mutants lacking the carboxyl terminus and thus mimicking the intermediate fail to safeguard the folding route and spontaneously form fibrillar aggregates. The structure provides a detailed characterization of the non-native interactions stabilizing an aggregation-prone intermediate under native conditions and insight into how such an intermediate can derail folding and initiate fibrillation.

PubMed: 22517863
DOI: 10.1126/science.1214203

実験手法

SOLUTION NMR