DEFECTIVE CO-TRANSLATIONAL FORMATION OF DISULFIDE BONDS IN PROTEIN DISULFIDE-ISOMERASE-DEFICIENT MICROSOMES
DEFECTIVE CO-TRANSLATIONAL FORMATION OF DISULFIDE BONDS IN PROTEIN DISULFIDE-ISOMERASE-DEFICIENT MICROSOMES
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DOI：
10.1038/335649a0
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发表时间：
1988-10-13
期刊：
影响因子：
64.8
通讯作者：
FREEDMAN, RB
中科院分区：
文献类型：
--
作者：
BULLEID, NJ;FREEDMAN, RB
哺乳动物分泌蛋白和细胞表面蛋白中二硫键的形成发生在内质网的内腔中，并且被认为是由酶蛋白二硫键异构酶（PDI）1催化的。PDI的这种生理作用的证据是间接的，涉及到酶的细胞和组织分布，其发育行为和其催化特性invitro 2 -4。在生物合成过程中，二硫键结合蛋白的正确折叠或组装对PDI的明确要求尚未得到证实。我们制备了狗胰腺微粒体，其缺乏可溶性腔内蛋白（包括PDI），但仍然能够转运和加工体外合成的蛋白质5，6。以小麦贮藏蛋白γ-麦醇溶蛋白7体外合成过程中分子内二硫键的形成为模型，证明了这些微粒体在二硫键的共翻译形成中存在缺陷。用纯化的PDI重建这些微粒体可逆转该缺陷。
The formation of disulphide bonds in mammalian secretory and cell-surface proteins occurs in the lumen of the endoplasmic reticulum and is believed to be catalysed by the enzyme protein disulphide-isomerase (PDI)1. The evidence for this physiological role for PDI is circumstantial and relates to the cell and tissue distribution of the enzyme, its developmental behaviour and its catalytic properties invitro2–4. A clear requirement for PDI in the correct folding or assembly of disulphide-bonded proteins during biosynthesis has not been demonstrated. We have prepared dog pancreas microsomes which are deficient in soluble lumenal proteins, including PDI, but which are still able to translocate and process proteins synthesized invitro5,6. Using the formation of intramolecular disulphide bonds during the invitrosynthesis of γ-gliadin7, a wheat storage protein, as a model, we have demonstrated that these microsomes are defective in co-translational formation of disulphide bonds. Reconstitution of these microsomes with purified PDI reverses this defect.