内质网中新合成蛋白质的错误折叠与聚集。
Misfolding and aggregation of newly synthesized proteins in the endoplasmic reticulum.
作者信息
Marquardt T, Helenius A
机构信息
Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06510.
出版信息
J Cell Biol. 1992 May;117(3):505-13. doi: 10.1083/jcb.117.3.505.
Abstract
As a part of our studies on the folding of glycoproteins in the ER, we analyzed the fate of viral glycoproteins that have misfolded either spontaneously or through inhibition of N-linked glycosylation. Newly synthesized Semliki Forest virus spike glycoproteins E1 and p62 and influenza hemagglutinin were studied in infected and transfected tissue culture cells. Misfolded proteins aggregated in less than 1 min after release from polysomes and aberrant interchain disulfide bonds were formed immediately. When more than one protein was misfolded, mixed aggregates were generated. This indicated that the formation of complexes was nonspecific, random, and not restricted to products from single polysomes. The size of the aggregates varied from small oligomers to complexes of several million daltons. BiP was associated noncovalently with the aggregates and with some of the nonaggregated products. We conclude that aggregation reflects the poor solubility of incompletely folded polypeptide chains.
摘要
作为我们对内质网中糖蛋白折叠研究的一部分，我们分析了自发错误折叠或通过抑制N-连接糖基化而错误折叠的病毒糖蛋白的命运。在感染和转染的组织培养细胞中研究了新合成的辛德毕斯病毒刺突糖蛋白E1和p62以及流感血凝素。错误折叠的蛋白质在从多核糖体释放后不到1分钟内就聚集在一起，并立即形成异常的链间二硫键。当一种以上的蛋白质错误折叠时，就会产生混合聚集体。这表明复合物的形成是非特异性的、随机的，并且不限于单个多核糖体的产物。聚集体的大小从小寡聚体到数百万道尔顿的复合物不等。BiP与聚集体以及一些未聚集的产物非共价结合。我们得出结论，聚集反映了不完全折叠的多肽链的低溶解度。
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