Intra- and Intermolecular β-Pleated Sheet Formation in Glutamine-repeat Inserted Myoglobin as a Model for Polyglutamine Diseases*
Intra- and Intermolecular β-Pleated Sheet Formation in Glutamine-repeat Inserted Myoglobin as a Model for Polyglutamine Diseases*
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谷氨酰胺重复插入肌红蛋白中分子内和分子间 β-折叠片的形成作为多谷氨酰胺疾病的模型*
DOI：
10.1074/jbc.m107502200
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
N. Nukina
中科院分区：
文献类型：
--
作者：
Motomasa Tanaka;I. Morishima;T. Akagi;T. Hashikawa;N. Nukina
扩张的聚谷氨酰胺的异常结构可能参与了CAG重复疾病聚集体的形成。为了阐明扩展的聚谷氨酰胺的结构性质，我们制备了抹香鲸肌红蛋白(Mb)突变体，在C和D螺旋之间的角落插入了12、28、35和50个重复的谷氨酰胺(分别为Gln12、Gln28、Gln35和Gln50)。圆二色谱和红外光谱表明，在Gln28、Gln35和Gln50Mb中被单抗1C2识别的扩展聚谷氨酰胺形成了反平行的β折叠片状结构。Gln50Mb聚集体由分子间反平行的β折叠片层组成。荧光和核磁共振氢谱显示Gln35和Gln50 Mb的蛋白质表面部分展开，尽管蛋白质核心的结构变化很小。目前的结果表明，蛋白质表面暴露的膨化聚谷氨酰胺的波动β折叠片层通过分子间相互作用促进了聚集体的形成。本研究首次建立并表征了聚谷氨酰胺病的分子模型的结构性质，在该模型中，不同长度的聚谷氨酰胺包括病理上扩展的谷氨酰胺重复序列被插入到结构已知的蛋白质中。
An aberrant structure of the expanded polyglutamine might be involved in the formation of aggregates in CAG repeat diseases. To elucidate structural properties of the expanded polyglutamine, we prepared sperm whale myoglobin (Mb) mutants, in which 12, 28, 35, and 50 repeats of glutamine were inserted at the corner between the C and D helices (Gln12, Gln28, Gln35, and Gln50, respectively). Circular dichroism and IR spectroscopies showed that the expanded polyglutamine, which was recognized by the monoclonal antibody 1C2 in Gln28, Gln35, and Gln50 Mb forms an antiparallel β-pleated sheet structure. Gln50 Mb aggregates were found to comprise an intermolecular antiparallel β-pleated sheet. Fluorescence together with 1H NMR spectra revealed partial unfolding of the protein surface in Gln35 and Gln50 Mb, although the structural changes in the protein core were rather small. The present results indicate that the fluctuating β-pleated sheet of the expanded polyglutamine exposed on the protein surface facilitates the formation of aggregates through intermolecular interactions. The present study has first established and characterized structural properties of a molecular model for polyglutamine diseases in which various lengths of polyglutamine including a pathologically expanded glutamine repeat were inserted into a structurally known protein.
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影响因子：
56.9
作者：
JENNINGS, PA;WRIGHT, PE
通讯作者：
WRIGHT, PE
谷氨酰胺重复序列的掺入使蛋白质寡聚化：对神经退行性疾病的影响。
DOI：
10.1073/pnas.92.14.6509
发表时间：
1995
影响因子：
11.1
作者：
Stott,K;Blackburn,JM;Butler,PJ;Perutz,M
通讯作者：
Perutz,M
基于 1H NMR 检测到的铁偶极场，确定 E7 His-->Val 氰基-met 肌红蛋白点突变体中血红素腔的溶液结构：血红素袋收缩的证据。
影响因子：
2.9
作者：
Rajarathnam,K;Qin,J;LaMar,GN;Chiu,ML;Sligar,SG
通讯作者：
Sligar,SG
DOI：
10.1073/pnas.84.24.8961
发表时间：
1987-12-01
影响因子：
11.1
作者：
SPRINGER, BA;SLIGAR, SG
通讯作者：
SLIGAR, SG