The ER membrane protein complex is a transmembrane domain insertase.

The ER membrane protein complex is a transmembrane domain insertase.
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ER膜蛋白复合物是跨膜结构域插入酶。

DOI:
10.1126/science.aao3099
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发表时间:
2018-01-26
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Hegde RS
Hegde RS
中科院分区:
其他
文献类型:
--
作者:
Guna A;Volkmar N;Christianson JC;Hegde RS

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将蛋白质插入细胞膜是一个重要的细胞过程。膜蛋白广泛的生物物理和拓扑多样性需要多个尚未完全确定的插入途径。在这里,我们发现已知的膜插入途径无法有效地与具有中等疏水性跨膜结构域的尾部锚定膜蛋白结合。相反,这些蛋白质在细胞质中被钙调蛋白保护。钙调蛋白的动态释放允许对内质网(ER)进行采样,其中保守的 ER 膜蛋白复合物(EMC)被证明对于体外和细胞内的有效插入至关重要。合成脂质体中的纯化 EMC 催化其底物插入重构系统中。因此,EMC 是一种跨膜结构域插入酶,这一功能可以解释其在生物体中广泛的多效性膜相关表型。
Insertion of proteins into membranes is an essential cellular process. The extensive biophysical and topological diversity of membrane proteins necessitates multiple insertion pathways that remain incompletely defined. Here we found that known membrane insertion pathways fail to effectively engage tail-anchored membrane proteins with moderately hydrophobic transmembrane domains. These proteins are instead shielded in the cytosol by calmodulin. Dynamic release from calmodulin allowed sampling of the endoplasmic reticulum (ER), where the conserved ER membrane protein complex (EMC) was shown to be essential for efficient insertion in vitro and in cells. Purified EMC in synthetic liposomes catalyzed the insertion of its substrates in a reconstituted system. Thus, EMC is a transmembrane domain insertase, a function that may explain its widely pleiotropic membrane-associated phenotypes across organisms.
DOI: 10.1016/j.celrep.2017.12.006
发表时间: 2017-12-26
期刊: Cell reports
影响因子: 8.8
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