SEC12 ENCODES A GUANINE-NUCLEOTIDE-EXCHANGE FACTOR ESSENTIAL FOR TRANSPORT VESICLE BUDDING FROM THE ER
SEC12 ENCODES A GUANINE-NUCLEOTIDE-EXCHANGE FACTOR ESSENTIAL FOR TRANSPORT VESICLE BUDDING FROM THE ER
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DOI：
10.1038/365347a0
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发表时间：
1993-09-23
期刊：
影响因子：
64.8
通讯作者：
SCHEKMAN, R
中科院分区：
文献类型：
--
作者：
BARLOWE, C;SCHEKMAN, R
在酵母中，II 型整合膜糖蛋白对于内质网 (ER) 中的运输囊泡出芽至关重要，由 SEC12 编码（参考文献 1-3）。 SAR1 被发现是 sec12-1ts 菌株的多拷贝复制抑制因子，编码 M(r) 21,000 (21K) 的 GTPase，这对于 ER4,5 的囊泡出芽也是必需的。 Sar1 是一种外周相关膜蛋白，在含有升高水平的 Sec12 蛋白的细胞中显示出增强的膜结合（参考文献 6、7）。我们在此表明，Sec12 的纯化片段可促进鸟嘌呤核苷酸从 Sar1 解离，而纯化的突变体 Sec12-1 仅具有野生型活性的 15%。 Sar1 的 GTP 水解不会被 Sec12 增强，但会被 Sec12 和 Sec23（一种针对 Sar1 的 GTP 酶激活蛋白）混合物刺激超过 50 倍（参考文献 8）。我们认为 Sec12 在将 Sar1 招募到 ER 膜上囊泡形成位点的过程中催化 Sar1 鸟嘌呤核苷酸交换。
IN yeast a type II integral membrane glycoprotein that is essential for transport vesicle budding from the endoplasmic reticulum (ER) is encoded by SEC12 (refs 1-3). SAR1 was discovered as a multi-copy copy suppressor of the sec12-1ts strain and encodes a GTPase of M(r) 21,000 (21K) also essential for vesicle budding from the ER4,5. Sar1 is a peripherally associated membrane protein which shows enhanced membrane binding in cells containing elevated levels of Sec12 protein (refs 6, 7). We show here that a purified fragment of Sec12 promotes guanine-nucleotide dissociation from Sar1 whereas the purified mutant Sec12-1 has only 15% of the wild-type activity. GTP hydrolysis by Sar1 is not enhanced by Sec12, but is stimulated more than 50-fold by a mixture of Sec12 and Sec23, a GTPase-activating protein specific for Sar1 (ref. 8). We propose that Sec12 catalyses Sar1 guanine-nucleotide exchange in a process that recruits Sar1 to a vesicle formation site on the ER membrane.