Yos9p detects and targets misfolded glycoproteins for ER-associated degradation
Yos9p detects and targets misfolded glycoproteins for ER-associated degradation
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DOI：
10.1016/j.molcel.2005.08.010
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发表时间：
2005-09-16
期刊：
影响因子：
16
通讯作者：
Ng, DTW
中科院分区：
文献类型：
--
作者：
Kim, W;Spear, ED;Ng, DTW
内质网(ER)质量控制机制监测新生分泌多肽和膜多肽的折叠。未成熟的分子活跃地保留在折叠隔间，而不能折叠的蛋白质被转移到依赖蛋白酶的降解途径。我们报道，内质网质量控制的一个关键途径是由Yos9p和Htm1/Mnl1p组成的两个凝集素受体系统，该系统识别嵌入底物的N-连接的糖链信号。这一途径识别以腔为导向的可溶性和膜蛋白决定因素。Yos9P直接与底物结合以区分错误折叠的蛋白质和折叠的蛋白质。显示胞质决定簇的底物可以独立于该系统被降解。我们的研究表明，机械发散的系统相互协作，防止错误折叠的蛋白质在分泌途径中通过和积累。
Encloplasmic reticulum (ER) quality control mechanisms monitor the folding of nascent secretory and membrane polypeptides. Immature molecules are actively retained in the folding compartment whereas proteins that fail to fold are diverted to proteasomedependent degradation pathways. We report that a key pathway of ER quality control consists of a two-lectin receptor system consisting of Yos9p and Htm1/ Mnl1p that recognizes N-linked glycan signals embedded in substrates. This pathway recognizes lumenally oriented determinants of soluble and membrane proteins. Yos9p binds directly to substrates to discriminate misfolded from folded proteins. Substrates displaying cytosolic determinants can be degraded independently of this system. Our studies show that mechanistically divergent systems collaborate to guard against passage and accumulation of misfolded proteins in the secretory pathway.