EDEM1 recognition and delivery of misfolded proteins to the SEL1L-containing ERAD complex.
EDEM1 recognition and delivery of misfolded proteins to the SEL1L-containing ERAD complex.
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DOI：
10.1016/j.molcel.2009.05.018
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发表时间：
2009-06-12
期刊：
影响因子：
16
通讯作者：
Hebert, Daniel N.
中科院分区：
文献类型：
--
作者：
Cormier, James H.;Tamura, Taku;Sunryd, Johan C.;Hebert, Daniel N.
末端错误折叠或未组装的分泌蛋白留在内质网（ER）中，随后通过内质网相关降解（ERAD）途径被清除。ERAD底物的降解涉及N - 连接聚糖的甘露糖修剪，然而底物识别以及分选进入ERAD途径的机制尚不明确。EDEM1（内质网降解增强α - 甘露糖苷酶样1蛋白）被认为在内质网相关降解底物的信号传导或识别中起作用。我们发现EDEM1以不依赖聚糖的方式特异性结合非天然蛋白质。用基夫碱抑制甘露糖苷酶活性，或者通过突变破坏EDEM1的甘露糖苷酶样结构域，对EDEM1底物结合没有影响，但会减弱其与内质网膜衔接蛋白SEL1L的结合。这些结果支持一种模型，即EDEM1结合非天然蛋白质，并利用其甘露糖苷酶样结构域将异常蛋白质靶向含有SEL1L的内质网膜错位和泛素化复合物。
Terminally misfolded or unassembled secretory proteins are retained in the endoplasmic reticulum (ER) and subsequently cleared by the ER-associated degradation (ERAD) pathway. The degradation of ERAD substrates involves mannose trimming of N-linked glycans, however the mechanisms of substrate recognition and sorting to the ERAD pathway are poorly defined. EDEM1 (ER degradation-enhancing α-mannosidase-like 1 protein) has been proposed to play a role in ERAD substrate signaling or recognition. We show that EDEM1 specifically binds non-native proteins in a glycan-independent manner. Inhibition of mannosidase activity with kifunensine or disruption of the EDEM1 mannosidase-like domain by mutation had no effect on EDEM1 substrate binding, but diminished its association with the ER membrane adapter protein, SEL1L. These results support a model whereby EDEM1 binds non-native proteins and uses its mannosidase-like domain to target aberrant proteins to the ER membrane dislocation and ubiquitination complex containing SEL1L.
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DOI：
10.1073/pnas.0805371105
发表时间：
2008-08-26
影响因子：
11.1
作者：
Mueller, Britta;Klemm, Elizabeth J.;Ploegh, Hidde L.
通讯作者：
Ploegh, Hidde L.
影响因子：
4
作者：
Svedine, S;Wang, T;Hebert, DN
通讯作者：
Hebert, DN
影响因子：
4.8
作者：
Liu, Y;Choudhury, P;Sifers, RN
通讯作者：
Sifers, RN
影响因子：
64.5
作者：
HEBERT, DN;FOELLMER, B;HELENIUS, A
通讯作者：
HELENIUS, A
影响因子：
56.9
作者：
Oda, Y;Hosokawa, N;Nagata, K
通讯作者：
Nagata, K