EFFICIENT CATALYSIS OF DISULFIDE BOND REARRANGEMENTS BY PROTEIN DISULFIDE-ISOMERASE
EFFICIENT CATALYSIS OF DISULFIDE BOND REARRANGEMENTS BY PROTEIN DISULFIDE-ISOMERASE
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DOI：
10.1038/365185a0
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发表时间：
1993-09-09
期刊：
影响因子：
64.8
通讯作者：
KIM, PS
中科院分区：
文献类型：
--
作者：
WEISSMAN, JS;KIM, PS
蛋白质二硫键异构酶（PDI）1，2是一种高度丰富和普遍存在的真核蛋白，对酵母中的生存力至关重要3，4。尽管PDI被认为在蛋白质生物合成期间催化二硫键形成和异构化，但先前已发现PDI对体外蛋白质的氧化折叠速率仅具有中等影响（约25倍）。此外，PDI还涉及几种明显无关的细胞功能3。例如，PDI是脯氨酰4-羟化酶5的β-亚基，并且是甘油三酯转移复合物6的一部分。牛胰胰蛋白酶抑制剂（BPTI）的氧化折叠在体外缓慢且低效7 -11。在这里，我们报告说，PDI增加了3000 - 6000倍的动力学捕获的BPTI折叠中间体，其中天然结构阻碍二硫键形成的折叠率。相比之下，PDI对在不存在PDI的情况下容易氧化的中间体中二硫键形成的速率仅具有小的影响。这些结果表明，PDI的一个重要功能是催化二硫键的形成和重排动力学捕获，结构折叠中间体。
PROTEIN disulphide isomerase (PDI)1,2 is a highly abundant and ubiquitous eukaryotic protein that is essential for viability in yeast3,4. Although PDI is thought to catalyse disulphide bond formation and isomerization during protein biosynthesis, PDI has been found previously to have only moderate effects (approximately 25-fold) on the rate of oxidative folding of proteins in vitro. In addition, PDI has been implicated in several apparently unrelated cellular functions3. For example, PDI is the beta-subunit of prolyl 4-hydroxylase 5 and is part of the trigylceride transfer complex6. The oxidative folding of bovine pancreatic trypsin inhibitor (BPTI) is slow and inefficient in vitro7-11. Here we report that PDI increases by a factor of 3,000-6,000 the rates of folding of kinetically trapped BPTI folding intermediates, in which native structure impedes disulphide bond formation. By contrast, PDI has only small effects on the rate of disulphide bond formation in intermediates that are oxidized readily in the absence of PDI. These results suggest that an important function of PDI is to catalyse disulphide bond formation and rearrangements within kinetically trapped, structured folding intermediates.