当前位置: X-MOL 学术Curr. Biol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Pre-emptive Quality Control of a Misfolded Membrane Protein by Ribosome-Driven Effects.
Current Biology ( IF 8.1 ) Pub Date : 2020-01-10 , DOI: 10.1016/j.cub.2019.12.060
Ramya Lakshminarayan 1 , Ben P Phillips 2 , Imogen L Binnian 2 , Natalia Gomez-Navarro 2 , Norberto Escudero-Urquijo 3 , Alan J Warren 3 , Elizabeth A Miller 4
Affiliation  

Cells possess multiple mechanisms that protect against the accumulation of toxic aggregation-prone proteins. Here, we identify a pre-emptive pathway that reduces synthesis of membrane proteins that have failed to properly assemble in the endoplasmic reticulum (ER). We show that loss of the ER membrane complex (EMC) or mutation of the Sec61 translocon causes reduced synthesis of misfolded forms of the yeast ABC transporter Yor1. Synthesis defects are rescued by various ribosomal mutations, as well as by reducing cellular ribosome abundance. Genetic and biochemical evidence point to a ribosome-associated quality-control pathway triggered by ribosome collisions when membrane domain insertion and/or folding fails. In support of this model, translation initiation also contributes to synthesis defects, likely by modulating ribosome abundance on the message. Examination of translation efficiency across the yeast membrane proteome revealed that polytopic membrane proteins have relatively low ribosome abundance, providing evidence for translational tuning to balance protein synthesis and folding. We propose that by modulating translation rates of poorly folded proteins, cells can pre-emptively protect themselves from potentially toxic aberrant transmembrane proteins.

中文翻译:

通过核糖体驱动效应对错误折叠的膜蛋白进行先发制人的质量控制。

细胞具有多种机制来防止有毒易聚集的蛋白质的积累。在这里,我们确定了一种先发制人的途径,可减少未能在内质网 (ER) 中正确组装的膜蛋白的合成。我们表明,ER 膜复合物 (EMC) 的丢失或 Sec61 易位子的突变导致酵母 ABC 转运蛋白 Yor1 的错误折叠形式的合成减少。各种核糖体突变以及减少细胞核糖体丰度可以挽救合成缺陷。遗传和生化证据表明,当膜结构域插入和/或折叠失败时,核糖体碰撞会触发核糖体相关的质量控制途径。为了支持这个模型,翻译起始也会导致合成缺陷,可能是通过调节信息上的核糖体丰度。跨酵母膜蛋白质组的翻译效率检查表明,多面体膜蛋白的核糖体丰度相对较低,为平衡蛋白质合成和折叠的翻译调节提供了证据。我们建议通过调节折叠不良的蛋白质的翻译速率,细胞可以先发制人地保护自己免受潜在毒性异常跨膜蛋白的侵害。
更新日期:2020-01-17
down
wechat
bug