NACP, a protein implicated in Alzheimer's disease and learning, is natively unfolded
NACP, a protein implicated in Alzheimer's disease and learning, is natively unfolded
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DOI：
10.1021/bi961799n
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发表时间：
1996-10-29
期刊：
影响因子：
2.9
通讯作者：
Lansbury, PT
中科院分区：
文献类型：
--
作者：
Weinreb, PH;Zhen, WG;Lansbury, PT
“阿尔茨海默病淀粉样斑块的非Aβ成分”(NAG)是阿尔茨海默病(AD)神经性斑块中不可溶的纤维核心的一种次要的多肽成分。NAC淀粉样蛋白是主要的AD淀粉样蛋白Aβ1-40聚合的种子。NAC来源于一个14 kDa的前体蛋白，命名为NACP，是一个高度保守的热稳定的脑特异性酸性蛋白家族的成员，已被认为参与突触的形成和/或稳定。NACP也被建议在AD中发挥作用。我们在这里提出了一个人NACP的构象分析。与分子量相近的球状蛋白相比，NACP具有更大的斯托克斯半径(34埃)，但沉降速度较慢(S(20，w)=1.7s)，表明天然蛋白被拉长。圆二色谱(CD)和傅里叶变换红外光谱(FTIR)表明NACP中没有大量的二级结构，而圆二色谱和紫外光谱表明NACP中没有疏水核心。NACP的构象性质在沸腾过程中保持不变，与浓度、pH、盐和化学变性剂无关。这些特征表明，NACP作为一种快速平衡的延伸构象的混合物而存在，并且是一类天然未折叠的蛋白质的代表，其中许多蛋白质增强了蛋白质之间的相互作用。
The ''non-A beta component of Alzheimer's disease amyloid plaque'' (NAG) 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 Angstrom) but sedimented more slowly (s(20,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.