Rapid amyloid fiber formation from the fast-folding WW domain FBP28
Rapid amyloid fiber formation from the fast-folding WW domain FBP28
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DOI：
10.1073/pnas.1333907100
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发表时间：
2003-08-19
影响因子：
11.1
通讯作者：
Fersht, AR
中科院分区：
文献类型：
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作者：
Ferguson, N;Berriman, J;Fersht, AR
WW结构域是含有三链反平行β折叠的小蛋白质。40个残基的鼠FBP28 WW结构域在生理温度和pH下迅速形成旋转的带状原纤维，具有典型的淀粉样原纤维的形态。这些带状物异常宽且排列有序，非常适合结构研究。它们的X射线和电子衍射图显示了交叉β衍射特征的特征性淀粉样蛋白纤维0.47 nm反射。常规和电子低温显微镜都清楚地表明，带状物由许多2.5 nm宽的平行于纤维长轴的亚丝组成。沿每根细丝中心沿着有一个密度较低的区域。这些细丝的横向关联产生扭曲的，通常是相互连接的，高达40纳米宽和许多微米长的片材。螺旋的节距从60至320 nm变化，取决于带的宽度。野生型FBP28纤维是在其他研究中观察到多指数折叠动力学的条件下形成的，这归因于折叠机制的变化。更有可能的是，这些阶段是由这里观察到的非途径聚集的初始事件引起的。
The WW domains are small proteins that contain a three-stranded, antiparallel beta-sheet. The 40-residue murine FBP28 WW domain rapidly formed twirling ribbon-like fibrils at physiological temperature and pH, with morphology typical of amyloid fibrils. These ribbons were unusually wide and well ordered, making them highly suitable for structural studies. Their x-ray and electron-diffraction patterns displayed the characteristic amyloid fiber 0.47-nm reflection of the cross-beta diffraction signature. Both conventional and electron cryomicroscopy showed clearly that the ribbons were composed of many 2.5-nm-wide subfilaments that ran parallel to the long axis of the fiber. There was a region of lower density along the center of each filament. Lateral association of these filaments generated twisted, often interlinked, sheets up to 40 nm wide and many microns in length. The pitch of the helix varied from 60 to 320 nm, depending on the width of the ribbon. The wild-type FBP28 fibers were formed under conditions in which multiexponential folding kinetics is observed in other studies and which was attributed to a change in the mechanism of folding. It is more likely that those phases result from initial events in the off-pathway aggregation observed here.