Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, The Biomedical Centre, 751 23 Uppsala, Sweden.
Biochem Biophys Res Commun. 2010 Nov 19;402(3):515-8. doi: 10.1016/j.bbrc.2010.10.062. Epub 2010 Oct 28.
Amyloid consists of β-sheet polymers and is associated with disease and with functional assemblies. Amyloid-forming proteins differ widely in native structures and sequences. We describe here how conformational preferences of non-polar amino acid residues can affect amyloid formation. The most non-polar residues promote either β-strands (Val, Ile, Phe, and Cys, VIFC) or α-helices (Leu, Ala, and Met, LAM), while the most polar residues promote only α-helices. For 12 proteins associated with disease, the localizations of the amyloid core regions are known. Eleven of these contain segments that are biased for VIFC, but essentially lack segments that are biased for LAM. For the amyloid β-peptide associated with Alzheimer's disease and an amyloidogenic fragment of the prion protein, observed effects of mutations support that VIFC bias favors formation of β-sheet aggregates and amyloid, while LAM bias prevents it. VIFC and LAM profiles combine information on secondary structure propensities and polarity, and add a simple criterion to the prediction of amyloidogenic regions.
淀粉样蛋白由β-折叠聚合物组成，与疾病和功能组装有关。淀粉样蛋白形成蛋白在天然结构和序列上差异很大。我们在这里描述了非极性氨基酸残基的构象偏好如何影响淀粉样蛋白的形成。最非极性的残基促进β-折叠（Val、Ile、Phe 和 Cys，VIFC）或α-螺旋（Leu、Ala 和 Met，LAM），而最极性的残基仅促进α-螺旋。对于 12 种与疾病相关的蛋白质，已知淀粉样蛋白核心区域的定位。其中 11 个包含偏向 VIFC 的片段，但基本上缺乏偏向 LAM 的片段。对于与阿尔茨海默病相关的淀粉样β肽和朊病毒蛋白的淀粉样片段，观察到的突变影响支持 VIFC 偏向有利于β-折叠聚集体和淀粉样蛋白的形成，而 LAM 偏向则阻止其形成。VIFC 和 LAM 分布结合了二级结构倾向和极性的信息，并为淀粉样蛋白形成区域的预测增加了一个简单的标准。
