Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Int J Mol Sci. 2021 Dec 28;23(1):281. doi: 10.3390/ijms23010281.
Fidelity of protein targeting is essential for the proper biogenesis and functioning of organelles. Unlike replication, transcription and translation processes, in which multiple mechanisms to recognize and reject noncognate substrates are established in energetic and molecular detail, the mechanisms by which cells achieve a high fidelity in protein localization remain incompletely understood. Signal recognition particle (SRP), a conserved pathway to mediate the localization of membrane and secretory proteins to the appropriate cellular membrane, provides a paradigm to understand the molecular basis of protein localization in the cell. In this chapter, we review recent progress in deciphering the molecular mechanisms and substrate selection of the mammalian SRP pathway, with an emphasis on the key role of the cotranslational chaperone NAC in preventing protein mistargeting to the ER and in ensuring the organelle specificity of protein localization.
蛋白质靶向的保真度对于细胞器的正确生物发生和功能至关重要。与复制、转录和翻译过程不同，在这些过程中，已经在能量和分子细节上建立了多种识别和拒绝非同源底物的机制，而细胞实现蛋白质定位高保真度的机制仍未完全理解。信号识别颗粒 (SRP) 是一种保守途径，可介导膜和分泌蛋白定位到适当的细胞膜，为理解细胞中蛋白质定位的分子基础提供了范例。在本章中，我们回顾了破译哺乳动物 SRP 途径的分子机制和底物选择的最新进展，重点介绍了共翻译伴侣 NAC 在防止蛋白质错误靶向内质网和确保蛋白质定位的细胞器特异性方面的关键作用。
