Protein Synthesis in the Developing Neocortex at Near-Atomic Resolution Reveals Ebp1-Mediated Neuronal Proteostasis at the 60S Tunnel Exit.
Protein Synthesis in the Developing Neocortex at Near-Atomic Resolution Reveals Ebp1-Mediated Neuronal Proteostasis at the 60S Tunnel Exit.
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DOI：
10.1016/j.molcel.2020.11.037
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发表时间：
2021-01-21
期刊：
影响因子：
16
通讯作者：
Spahn CMT
中科院分区：
文献类型：
--
作者：
Kraushar ML;Krupp F;Harnett D;Turko P;Ambrozkiewicz MC;Sprink T;Imami K;Günnigmann M;Zinnall U;Vieira-Vieira CH;Schaub T;Münster-Wandowski A;Bürger J;Borisova E;Yamamoto H;Rasin MR;Ohler U;Beule D;Mielke T;Tarabykin V;Landthaler M;Kramer G;Vida I;Selbach M;Spahn CMT
蛋白质合成必须在发育中的神经系统中进行微调，作为基因表达的最后一个重要步骤。本研究探讨了神经发生过程中新皮层核糖体的结构，揭示了Ebp1作为一个高占用率的60 S肽隧道出口（TE）因子在蛋白质合成过程中，在近原子分辨率的冷冻电子显微镜（cryo-EM）。核糖体分析表明，Ebp1 - 60S结合是最高的起始密码子起始和N-末端肽延长，调节这些密码子的核糖体占用。膜靶向结构域出现在60 S隧道中，将SRP/Sec61募集到共享的结合位点，取代Ebp1。Ebp1在早期出生的神经干细胞（NSC）谱系中特别丰富，并调节神经元形态。Ebp1特别影响膜靶向细胞粘附分子（CAM）的合成，通过细胞培养物中氨基酸的脉冲稳定同位素标记（pSILAC）/生物正交非规范氨基酸标记（BONCAT）质谱（MS）进行测量。因此，Ebp1是蛋白质合成的核心组成部分，而核糖体TE是发育过程中神经元形态分子规范中基因表达控制的焦点。Kraushar等人以近原子分辨率可视化发育中的小鼠大脑中的蛋白质合成。Ebp1结合60S隧道出口，以调节翻译起始和N-末端肽延伸蛋白质组范围。ebp1在早期新生的新皮层神经干细胞中特别丰富，并调节神经元形态，影响细胞粘附分子的合成。
Protein synthesis must be finely tuned in the developing nervous system as the final essential step of gene expression. This study investigates the architecture of ribosomes from the neocortex during neurogenesis, revealing Ebp1 as a high-occupancy 60S peptide tunnel exit (TE) factor during protein synthesis at near-atomic resolution by cryoelectron microscopy (cryo-EM). Ribosome profiling demonstrated Ebp1-60S binding is highest during start codon initiation and N-terminal peptide elongation, regulating ribosome occupancy of these codons. Membrane-targeting domains emerging from the 60S tunnel, which recruit SRP/Sec61 to the shared binding site, displace Ebp1. Ebp1 is particularly abundant in the early-born neural stem cell (NSC) lineage and regulates neuronal morphology. Ebp1 especially impacts the synthesis of membrane-targeted cell adhesion molecules (CAMs), measured by pulsed stable isotope labeling by amino acids in cell culture (pSILAC)/bioorthogonal noncanonical amino acid tagging (BONCAT) mass spectrometry (MS). Therefore, Ebp1 is a central component of protein synthesis, and the ribosome TE is a focal point of gene expression control in the molecular specification of neuronal morphology during development. Kraushar et al. visualize protein synthesis in the developing mouse brain at near-atomic resolution. Ebp1 binds the 60S tunnel exit to regulate translation initiation and N-terminal peptide elongation proteome-wide. Ebp1 is particularly abundant in early-born neocortex neural stem cells and regulates neuronal morphology, impacting cell adhesion molecule synthesis.
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影响因子：
16.2
作者：
Cadwell, Cathryn R.;Bhaduri, Aparna;Mostajo-Radji, Mohammed A.;Keefe, Matthew G.;Nowakowski, Tomasz J.
通讯作者：
Nowakowski, Tomasz J.
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
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通讯作者：
Cowtan, K
影响因子：
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影响因子：
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作者：
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影响因子：
64.5
作者：
Behrmann E;Loerke J;Budkevich TV;Yamamoto K;Schmidt A;Penczek PA;Vos MR;Bürger J;Mielke T;Scheerer P;Spahn CM
通讯作者：
Spahn CM