Endoplasmic reticulum-associated degradation of a degron-containing polytopic membrane protein.
Endoplasmic reticulum-associated degradation of a degron-containing polytopic membrane protein.
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DOI：
10.3109/09687680903333839
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发表时间：
2009-12
影响因子：
--
通讯作者：
High S
中科院分区：
文献类型：
--
作者：
Ray-Sinha A;Cross BC;Mironov A;Wiertz E;High S
两个碱性氨基酸的存在下，战略性地位于一个单一的跨膜区域已被证明是作为一个信号的内质网相关的降解（ERAD）的几种多肽。相比之下，这种降解决定子基序在多位膜蛋白背景下的功能尚未建立。使用视蛋白作为一个模型系统，我们已经研究了在其七个跨膜（TM）跨度的第一个中插入降解决定子基序的后果。虽然这些碱性残基减少了靶向因子、信号识别颗粒与第一TM跨度的结合，但这对体外或体内的膜整合没有影响。这很可能反映了多个TM跨度的存在，这些跨度可以在新生视蛋白链中充当靶向信号。我们发现，降解决定子基序导致突变体视蛋白链在内质网的有效保留。突变体视蛋白多肽通过涉及E3泛素连接酶HRD 1作用的蛋白酶体途径降解。相比之下，野生型视蛋白即使在内质网处人工积累时也能长时间保持稳定。我们的结论是，一个单一的二元降解决定子基序是足以启动ER保留和随后的降解ostin通过ERAD途径。
The presence of two basic amino acids strategically located within a single spanning transmembrane region has previously been shown to act as a signal for the endoplasmic reticulum associated degradation (ERAD) of several polypeptides. In contrast, the functionality of this degron motif within the context of a polytopic membrane protein has not been established. Using opsin as a model system, we have investigated the consequences of inserting the degron motif in the first of its seven transmembrane (TM) spans. Whilst these basic residue reduce the binding of the targeting factor, signal recognition particle, to the first TM span, this has no effect on membrane integration in vitro or in vivo. This most likely reflects the presence of multiple TM spans that can act as targeting signals within in the nascent opsin chain. We find that the degron motif leads to the efficient retention of mutant opsin chains at the endoplasmic reticulum. The mutant opsin polypeptides are degraded via a proteasomal pathway that involves the actions of the E3 ubiquitin ligase HRD1. In contrast, wild-type opsin remains stable for a prolonged period even when artificially accumulated at the endoplasmic reticulum. We conclude that a single dibasic degron motif is sufficient to initiate both the ER retention and subsequent degradation of ospin via an ERAD pathway.
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DOI：
10.1073/pnas.91.9.4024
发表时间：
1994-04-26
影响因子：
11.1
作者：
KAUSHAL, S;RIDGE, KD;KHORANA, HG
通讯作者：
KHORANA, HG
影响因子：
4.8
作者：
Laird, V;High, S
通讯作者：
High, S
DOI：
10.1073/pnas.84.16.5783
发表时间：
1987-08-01
影响因子：
11.1
作者：
AUDIGIER, Y;FRIEDLANDER, M;BLOBEL, G
通讯作者：
BLOBEL, G
影响因子：
64.8
作者：
FRIEDLANDER, M;BLOBEL, G
通讯作者：
BLOBEL, G
DOI：
10.1016/j.biocel.2008.06.003
发表时间：
2008-01-01
影响因子：
4
作者：
Lass, Agnieszka;Kujawa, Marek;Wojcik, Cezary
通讯作者：
Wojcik, Cezary