2NNT

General structural motifs of amyloid protofilaments

2NNT の概要

• エントリーDOI: 10.2210/pdb2nnt/pdb
• 分子名称: Transcription elongation regulator 1 (1 entity in total)
• 機能のキーワード: fibre, beta-hairpin, fbp28 protofilament, ca150 second ww domain, protein fibril
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus: O14776
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 18496.14

構造登録者

Ferguson, N.,Becker, J.,Tidow, H.,Tremmel, S.,Sharpe, T.D.,Krause, G.,Flinders, J.,Petrovich, M.,Berriman, J.,Oschkinat, H.,Fersht, A.R. (登録日: 2006-10-24, 公開日: 2006-11-14, 最終更新日: 2023-12-27)

主引用文献

Ferguson, N.,Becker, J.,Tidow, H.,Tremmel, S.,Sharpe, T.D.,Krause, G.,Flinders, J.,Petrovich, M.,Berriman, J.,Oschkinat, H.,Fersht, A.R.
General structural motifs of amyloid protofilaments.
Proc.Natl.Acad.Sci.Usa, 103:16248-16253, 2006

PubMed Abstract: Human CA150, a transcriptional activator, binds to and is co-deposited with huntingtin during Huntington's disease. The second WW domain of CA150 is a three-stranded beta-sheet that folds in vitro in microseconds and forms amyloid fibers under physiological conditions. We found from exhaustive alanine scanning studies that fibrillation of this WW domain begins from its denatured conformations, and we identified a subset of residues critical for fibril formation. We used high-resolution magic-angle-spinning NMR studies on site-specific isotopically labeled fibrils to identify abundant long-range interactions between side chains. The distribution of critical residues identified by the alanine scanning and NMR spectroscopy, along with the electron microscopy data, revealed the protofilament repeat unit: a 26-residue non-native beta-hairpin. The structure we report has similarities to the hairpin formed by the A(beta)((1-40)) protofilament, yet also contains closely packed side-chains in a "steric zipper" arrangement found in the cross-beta spine formed from small peptides from the Sup35 prion protein. Fibrillation of unrelated amyloidogenic sequences shows the common feature of zippered repeat units that act as templates for fiber elongation.

PubMed: 17060612
DOI: 10.1073/pnas.0607815103

実験手法

SOLID-STATE NMR