SEL1L nucleates a protein complex required for dislocation of misfolded glycoproteins
SEL1L nucleates a protein complex required for dislocation of misfolded glycoproteins
复制标题
DOI：
10.1073/pnas.0805371105
复制
发表时间：
2008-08-26
影响因子：
11.1
通讯作者：
Ploegh, Hidde L.
中科院分区：
文献类型：
--
作者：
Mueller, Britta;Klemm, Elizabeth J.;Ploegh, Hidde L.
在内质网中未能通过质量控制的膜蛋白和分泌蛋白会被排放到细胞质中，并由蛋白酶体降解。这一过程中涉及的许多哺乳动物成分仍有待确定。我们对与SEL1L相互作用的蛋白质进行了生化搜索，SEL1L是哺乳动物HRD1连接酶复合物的一部分，参与底物识别。SEL1L对于人类巨细胞病毒US11蛋白使I类主要组织相容性复合体重链脱位至关重要。我们鉴定出AUP1、UBXD8、UBC6e和OS9是哺乳动物细胞中这种降解复合物在功能上的重要组成部分，通过对这些蛋白质的诱变和显性负性变体得到了证实。
Membrane and secretory proteins that fail to pass quality control in the endoplasmic reticulum are discharged into the cytosol and degraded by the proteasome. Many of the mammalian components involved in this process remain to be identified. We performed a biochemical search for proteins that interact with SEL1L, a protein that is part of the mammalian HRD1 ligase complex and involved in substrate recognition. SEL1L is crucial for dislocation of Class I major histocompatibility complex heavy chains by the human cytomegalovirus US11 protein. We identified AUP1, UBXD8, UBC6e, and OS9 as functionally important components of this degradation complex in mammalian cells, as confirmed by mutagenesis and dominant negative versions of these proteins.