Yoshida Hirotaka, Craxton Molly, Jakes Ross, Zibaee Shahin, Tavaré Richard, Fraser Graham, Serpell Louise C, Davletov Bazbek, Crowther R Anthony, Goedert Michel
MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, United Kingdom.
Biochemistry. 2006 Feb 28;45(8):2599-607. doi: 10.1021/bi051993m.
In humans, three genes encode the related alpha-, beta-, and gamma-synucleins, which function as lipid-binding proteins in vitro. They are being widely studied, mainly because of the central involvement of alpha-synuclein in a number of neurodegenerative diseases, including Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. In these diseases, the normally soluble alpha-synuclein assembles into abnormal filaments. Here, we have identified and characterized the synuclein gene family from the pufferfish Fugu rubripes. It consists of four genes, which encode alpha-, beta-, gamma1-, and gamma2-synucleins. They range from 113 to 127 amino acids in length and share many of the characteristics of human synucleins, including the presence of imperfect amino-terminal repeats of 11 amino acids, a hydrophobic middle region, and a negatively charged carboxy-terminus. All four synucleins are expressed in the Fugu brain. Recombinant Fugu synucleins exhibited differential liposome binding, which was strongest for alpha-synuclein, followed by beta-, gamma2-, and gamma1-synucleins. In assembly experiments, Fugu alpha-, gamma1-, and gamma2-synucleins formed filaments more readily than human alpha-synuclein. Fugu beta-synuclein, by contrast, failed to assemble in bulk. Filament assembly of synucleins was directly proportional to their degree of hydrophobicity and their tendency to form beta-sheet structure, and correlated inversely with their net charge.
在人类中，有三个基因编码相关的α-、β-和γ-突触核蛋白，它们在体外作为脂质结合蛋白发挥作用。它们受到广泛研究，主要是因为α-突触核蛋白在包括帕金森病、路易体痴呆和多系统萎缩在内的多种神经退行性疾病中起核心作用。在这些疾病中，通常可溶的α-突触核蛋白组装成异常细丝。在这里，我们从河豚红鳍东方鲀中鉴定并表征了突触核蛋白基因家族。它由四个基因组成，分别编码α-、β-、γ1-和γ2-突触核蛋白。它们的长度在113至127个氨基酸之间，具有人类突触核蛋白的许多特征，包括存在11个氨基酸的不完全氨基末端重复序列、一个疏水的中间区域和一个带负电荷的羧基末端。所有四种突触核蛋白都在河豚大脑中表达。重组河豚突触核蛋白表现出不同的脂质体结合能力，其中α-突触核蛋白最强，其次是β-、γ2-和γ1-突触核蛋白。在组装实验中，河豚α-、γ1-和γ2-突触核蛋白比人类α-突触核蛋白更容易形成细丝。相比之下，河豚β-突触核蛋白不能大量组装。突触核蛋白的细丝组装与其疏水性程度和形成β-折叠结构的倾向成正比，与它们的净电荷成反比。
