ジャーナル: Proc Natl Acad Sci U S A / 年: 2013 タイトル: Atomic structure and hierarchical assembly of a cross-β amyloid fibril. 著者: Anthony W P Fitzpatrick / Galia T Debelouchina / Marvin J Bayro / Daniel K Clare / Marc A Caporini / Vikram S Bajaj / Christopher P Jaroniec / Luchun Wang / Vladimir Ladizhansky / Shirley A ...著者: Anthony W P Fitzpatrick / Galia T Debelouchina / Marvin J Bayro / Daniel K Clare / Marc A Caporini / Vikram S Bajaj / Christopher P Jaroniec / Luchun Wang / Vladimir Ladizhansky / Shirley A Müller / Cait E MacPhee / Christopher A Waudby / Helen R Mott / Alfonso De Simone / Tuomas P J Knowles / Helen R Saibil / Michele Vendruscolo / Elena V Orlova / Robert G Griffin / Christopher M Dobson / 要旨: The cross-β amyloid form of peptides and proteins represents an archetypal and widely accessible structure consisting of ordered arrays of β-sheet filaments. These complex aggregates have ...The cross-β amyloid form of peptides and proteins represents an archetypal and widely accessible structure consisting of ordered arrays of β-sheet filaments. These complex aggregates have remarkable chemical and physical properties, and the conversion of normally soluble functional forms of proteins into amyloid structures is linked to many debilitating human diseases, including several common forms of age-related dementia. Despite their importance, however, cross-β amyloid fibrils have proved to be recalcitrant to detailed structural analysis. By combining structural constraints from a series of experimental techniques spanning five orders of magnitude in length scale--including magic angle spinning nuclear magnetic resonance spectroscopy, X-ray fiber diffraction, cryoelectron microscopy, scanning transmission electron microscopy, and atomic force microscopy--we report the atomic-resolution (0.5 Å) structures of three amyloid polymorphs formed by an 11-residue peptide. These structures reveal the details of the packing interactions by which the constituent β-strands are assembled hierarchically into protofilaments, filaments, and mature fibrils.
濃度: 1 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES
試料支持
詳細: holey carbon films (R2/2, QuantifoilMicro Tools GmbH, Jena, Germany)
急速凍結
装置: HOMEMADE PLUNGER / 凍結剤: ETHANE / Temp: 99 K / 湿度: 95 % 詳細: Fibrils were applied to holey carbon films that were immediately plunge-frozen at liquid nitrogen temperature.
手法: Common crossovers / 解像度: 12.7 Å / 解像度の算出法: FSC 0.5 CUT-OFF / 粒子像の数: 82 / ピクセルサイズ(公称値): 1.8 Å / ピクセルサイズ(実測値): 1.8 Å 詳細: The particles were selected using an automatic selection program. クラス平均像の数: 18 / 対称性のタイプ: HELICAL
精密化ステップ
サイクル: LAST
タンパク質
核酸
リガンド
溶媒
全体
原子数
680
0
0
0
680
NMR software
名称
開発者
分類
CNSSOLVE
Brunger, Adams, Clore, Gros, NilgesandRead
構造決定
CNSSOLVE
Brunger, Adams, Clore, Gros, NilgesandRead
精密化
精密化
手法: simulated annealing / ソフトェア番号: 1
代表構造
選択基準: lowest energy
NMRアンサンブル
コンフォーマー選択の基準: structures with the least restraint violations 計算したコンフォーマーの数: 100 / 登録したコンフォーマーの数: 1