Atomic force microscopy analysis of the Huntington protein nanofibril formation
Atomic force microscopy analysis of the Huntington protein nanofibril formation
复制标题
DOI：
10.1016/j.disamonth.2005.08.006
复制
发表时间：
2005-06-01
影响因子：
4
通讯作者：
Lyubchenko, YL
中科院分区：
文献类型：
--
作者：
Dahlgren, PR;Karymov, MA;Lyubchenko, YL
背景亨廷顿氏病是一种常染色体显性进行性神经变性疾病，与亨廷顿蛋白htt的外显子1中的多聚谷氨酰胺序列的急剧扩增相关，所述扩增导致纤维的细胞质甚至核聚集。在突变外显子1蛋白的谷胱甘肽-S-转移酶融合蛋白裂解后，自发形成大的聚集体。AFM数据显示，与淀粉样β肽和α-突触核蛋白等蛋白质组装的纤维不同，htt形成的纤维具有广泛的分支形态特征。即使在htt自组装的早期阶段也可以观察到分支，但在聚集的后期阶段效果更加明显。我们还发现，融合的htt与绿色荧光蛋白不改变分支型的形态特征的aggregate. CONCLUSIONSPonion的基础上所获得的结果，我们提出了一个模型htt fietization，解释分支的形态特征的聚集体。
BACKGROUNDHuntington's disease is an autosomal dominant progressive neurodegenerative disease associated with dramatic expansion of a polyglutamine sequence in exon 1 of the huntingtin protein htt that leads to cytoplasmic, and even nuclear aggregation of fibrils.METHODSWe have studied the in vitro fibril formation of mutant exon 1, and the shorter wild-type exon 1, with use of atomic force microscopy (AFM).RESULTSLarge aggregates are formed spontaneously after cleavage of the glutathione-S-transferase fusion protein of the mutant exon 1 protein. The AFM data showed that, unlike fibrils assembled by such proteins as amyloid β-peptide and α-synuclein, htt forms fibrils with extensive branched morphologic features. Branching can be observed even at earlier stages of the htt self-assembly, but the effect is much more pronounced at late stages of aggregation. We also found that fusing of htt with green fluorescent protein does not change the branched-type morphologic features of the aggregates.CONCLUSIONSOn the basis of the results obtained, we propose a model for htt fibrillization that explains branched morphologic features of the aggregates.