Brodsky Jeffrey L, Engelman Donald M, Hendershot Linda M, Piana-Agostinetti Stefano, Sommer Thomas
University of Pittsburgh.
Yale University.
Fac Rev. 2022 Oct 5;11:29. doi: 10.12703/r-01-0000018. eCollection 2022.
Proteins that are expressed on membrane surfaces or secreted are involved in all aspects of cellular and organismal life, and as such require extremely high fidelity during their synthesis and maturation. These proteins are synthesized at the endoplasmic reticulum (ER) where a dedicated quality control system (ERQC) ensures only properly matured proteins reach their destinations. An essential component of this process is the identification of proteins that fail to pass ERQC and their retrotranslocation to the cytosol for proteasomal degradation. This study by Wu . reports a cryo-electron microscopy (cryo-EM) structure of the five-protein channel through which aberrant proteins are extracted from the ER, providing insights into how recognition of misfolded proteins is coupled to their transport through a hydrophobic channel that acts to thin the ER membrane, further facilitating their dislocation to the cytosol.
在细胞膜表面表达或分泌的蛋白质参与细胞和机体生命活动的方方面面，因此在其合成和成熟过程中需要极高的保真度。这些蛋白质在内质网（ER）中合成，内质网中有专门的质量控制系统（ERQC），以确保只有正确成熟的蛋白质才能到达其目的地。这一过程的一个重要组成部分是识别未能通过ERQC的蛋白质，并将其逆向转运到细胞质中进行蛋白酶体降解。吴等人的这项研究报告了一种五蛋白通道的冷冻电子显微镜（cryo-EM）结构，异常蛋白质通过该通道从内质网中被提取出来，这为深入了解错误折叠蛋白质的识别如何与它们通过疏水性通道的转运相耦合提供了线索，该疏水性通道可使内质网膜变薄，进一步促进它们向内质网的错位。
