The AAA ATPase p97 links peptide N-glycanase to the endoplasmic reticulum-associated E3 ligase autocrine motility factor receptor
The AAA ATPase p97 links peptide N-glycanase to the endoplasmic reticulum-associated E3 ligase autocrine motility factor receptor
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DOI：
10.1073/pnas.0602747103
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发表时间：
2006-05-30
影响因子：
11.1
通讯作者：
Lennarz, William J.
中科院分区：
文献类型：
--
作者：
Li, Guangtao;Zhao, Gang;Lennarz, William J.
小鼠肽N-聚糖酶（mPNGase）从错误折叠的糖蛋白和糖肽中切割N-聚糖链。以前，发现几种蛋白质与mPNGase直接相互作用;其中，发现mHR 23 B和mS 4都将mPNGase连接到蛋白酶体。在这项研究中，我们发现，细胞质蛋白mp 97参与形成一个三元复合物含有小鼠自分泌运动因子受体（mAMFR），mp 97，和mPNGase。这种组装募集靠近内质网（ER）膜的胞质mPNGase，错误折叠的糖蛋白被认为发生逆转位。除了ER膜相关的E3连接酶mAMFR外，还发现含有乌巴和UBX结构域的胞质蛋白mY 33 K也与mp 97直接相互作用。因此，含有mAMFR、mY 33 K、mp 97、mPNGase和mHR 23 B五种蛋白质的复合物在紧邻ER膜处形成，并用于偶联逆转位、泛素化和去糖基化的活性，从而将错误折叠的糖蛋白路由至蛋白酶体。
Mouse pepticle N-glycanase (mPNGase) cleaves the N-glycan chain from misfolded glycoproteins and glycopeptides. Previously, several proteins were found to directly interact with mPNGase; among them, both mHR23B and mS4 were found to link mPNGase to the proteasome. In this study, we found that the cytoplasmic protein mp97 participates in the formation of a ternary complex containing mouse autocrine motility factor receptor (mAMFR), mp97, and mPNGase. This assemblage recruits the cytosolic mPNGase close to the endoplasmic reticulum (ER) membrane, where the retrotranslocation of misfolded glycoproteins is thought to occur. In addition to the ER membrane-associated E3 ligase mAMFR, a cytosolic protein mY33K, containing both UBA and UBX domains, was found to also directly interact with mp97. Thus, a complex containing five proteins, mAMFR, mY33K, mp97, mPNGase, and mHR23B, is formed in close proximity to the ER membrane and serves to couple the activities of retrotranslocation, ubiquitination, and deglycosylation and, thereby, route misfolded glycoproteins to the proteasome.