Molecular mechanism of cargo recognition and handover by the mammalian signal recognition particle.
Molecular mechanism of cargo recognition and handover by the mammalian signal recognition particle.
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DOI：
10.1016/j.celrep.2021.109350
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发表时间：
2021-07-13
期刊：
影响因子：
8.8
通讯作者：
Ban N
中科院分区：
文献类型：
--
作者：
Jomaa A;Eitzinger S;Zhu Z;Chandrasekar S;Kobayashi K;Shan SO;Ban N
通过信号识别颗粒（SRP）靶向膜的共翻译蛋白是从细菌到人类的普遍保守的途径。在哺乳动物中，与细菌系统相比，SRP 及其受体 (SR) 具有许多额外的 RNA 特征和蛋白质成分，最近被证明发挥着调节作用。由于其复杂性，哺乳动物 SRP 靶向过程在机制上尚不清楚。特别是，目前尚不清楚SRP如何识别具有暴露信号序列的翻译核糖体以及SRP和SR的GTP酶活性如何受到调节。在这里，我们展示了 SRP 和 SRP·SR 与翻译核糖体复合物的电子冷冻显微镜结构。这些结构揭示了SRP与新出现的信号序列以及调节SRP·SR GTP酶活性的元件之间的特定分子相互作用。我们的结果揭示了真核生物特异性元件如何调节 SRP 依赖性蛋白靶向的早期和晚期的分子机制。乔玛等人。展示哺乳动物 SRP、SRP 受体和翻译核糖体的冷冻电镜结构。这些结构揭示了真核生物特异性特征在调节共翻译蛋白靶向内质网的早期和晚期的作用，并提出了货物识别和移交的模型。
Co-translational protein targeting to membranes by the signal recognition particle (SRP) is a universally conserved pathway from bacteria to humans. In mammals, SRP and its receptor (SR) have many additional RNA features and protein components compared to the bacterial system, which were recently shown to play regulatory roles. Due to its complexity, the mammalian SRP targeting process is mechanistically not well understood. In particular, it is not clear how SRP recognizes translating ribosomes with exposed signal sequences and how the GTPase activity of SRP and SR is regulated. Here, we present electron cryo-microscopy structures of SRP and SRP·SR in complex with the translating ribosome. The structures reveal the specific molecular interactions between SRP and the emerging signal sequence and the elements that regulate GTPase activity of SRP·SR. Our results suggest the molecular mechanism of how eukaryote-specific elements regulate the early and late stages of SRP-dependent protein targeting. Jomaa et al. present cryo-EM structures of mammalian SRP, SRP receptor, and the translating ribosome. The structures reveal the role of eukaryotic-specific features involved in regulating early and late stages of co-translational protein targeting to the endoplasmic reticulum and suggest a model for cargo recognition and handover.
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DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
7.8
作者：
GILMORE, R;WALTER, P;BLOBEL, G
通讯作者：
BLOBEL, G
DOI：
10.1126/science.1165971
发表时间：
2009-01-02
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Bradshaw N;Neher SB;Booth DS;Walter P
通讯作者：
Walter P
影响因子：
16.8
作者：
Hainzl, Tobias;Huang, Shenghua;Sauer-Eriksson, A. Elisabeth
通讯作者：
Sauer-Eriksson, A. Elisabeth
影响因子：
64.5
作者：
GORLICH, D;RAPOPORT, TA
通讯作者：
RAPOPORT, TA