Weinreb P H, Zhen W, Poon A W, Conway K A, Lansbury P T
Department of Chemistry, Massachusetts Institute of Technology, Cambridge 02139, USA.
Biochemistry. 1996 Oct 29;35(43):13709-15. doi: 10.1021/bi961799n.
The "non-A beta component of Alzheimer's disease amyloid plaque" (NAC) is a minor peptide component of the insoluble fibrillar core of the Alzheimer's disease (AD) neuritic plaque. NAC amyloid fibrils seed the polymerization of A beta 1-40, the major AD amyloid protein. NAC is derived from a 14 kDa precursor protein, designated NACP, a member of a highly conserved family of heat-stable brain-specific acidic proteins which have been suggested to be involved in synapse formation and/or stabilization. NACP has also been suggested to play a role in AD. We present herein a conformational analysis of human NACP. NACP has a much larger Stokes radius (34 A) but sedimented more slowly (s20,w = 1.7S) than globular proteins of similar molecular weight, indicating that the native protein is elongated. Circular dichroism (CD) and Fourier-transform infrared spectroscopy (FTIR) indicate the absence of significant amounts of secondary structure in NACP, while CD and ultraviolet spectroscopy suggest the lack of a hydrophobic core. The conformational properties of NACP were unchanged by boiling and were independent of concentration, pH, salt, and chemical denaturants. These features indicate that NACP exists as a mixture of rapidly equilibrating extended conformers and is representative of a class of "natively unfolded" proteins, many of which potentiate protein-protein interactions.
阿尔茨海默病淀粉样斑块的“非Aβ成分”（NAC）是阿尔茨海默病（AD）神经炎性斑块不溶性纤维状核心的一种次要肽成分。NAC淀粉样纤维引发了主要的AD淀粉样蛋白Aβ1-40的聚合。NAC来源于一种14 kDa的前体蛋白，称为NACP，它是一个高度保守的热稳定脑特异性酸性蛋白家族的成员，有人认为该家族参与突触形成和/或稳定。也有人认为NACP在AD中起作用。我们在此展示了人NACP的构象分析。NACP的斯托克斯半径（34 Å）大得多，但沉降速度比类似分子量的球状蛋白慢得多（s20,w = 1.7S），这表明天然蛋白是拉长的。圆二色性（CD）和傅里叶变换红外光谱（FTIR）表明NACP中不存在大量二级结构，而CD和紫外光谱表明缺乏疏水核心。NACP的构象性质在煮沸后不变，且与浓度、pH、盐和化学变性剂无关。这些特征表明NACP以快速平衡的伸展构象混合物形式存在，代表了一类“天然未折叠”的蛋白质，其中许多能增强蛋白质-蛋白质相互作用。
