美国哈佛医学院Eunyong Park、Sichen Shao等研究人员合作发现，内质网P5A-ATP酶是跨膜螺旋脱位酶。2020年9月25日出版的《科学》杂志发表了这一研究成果。

 

研究人员发现孤儿P5A-腺苷三磷酸酶（ATP酶）转运蛋白ATP13A1（酵母中的Spf1）与线粒体尾部锚定蛋白的跨膜片段（TM）直接相互作用。P5A-ATP酶活性介导从内质网（ER）提取错误靶向的蛋白质。酿酒酵母Spf1的冷冻电镜结构揭示了一个大的、可触及膜的底物结合袋，该袋交替面对ER内腔和胞质以及类似于α-螺旋TM的内源性底物。

 

这些结果表明，P5A-ATP酶可以使错误插入的疏水性螺旋错位，而其两侧是来自ER的短基本片段。P5A-ATP酶引起的TM脱位建立了另一类P型ATP酶底物，并可能纠正蛋白质靶向或拓扑生成中的错误。

 

据介绍，细胞器的身份取决于蛋白质组成。如何正确识别错误靶向的蛋白质并从细胞器中清除是不完全清楚的。 

 

附：英文原文

 

Title:The endoplasmic reticulum P5A-ATPase is a transmembrane helix dislocase

 

Author:Michael J. McKenna1,*, View ORCID ProfileSue Im Sim2,*, View ORCID ProfileAlban Ordureau1, Lianjie Wei1,†, View ORCID ProfileJ. Wade Harper

 

Issue&Volume:25 Sep 2020

 

Abstract: Organelle identity depends on protein composition. How mistargeted proteins are selectively recognized and removed from organelles is incompletely understood. Here, we found that the orphan P5A–adenosine triphosphatase (ATPase) transporter ATP13A1 (Spf1 in yeast) directly interacted with the transmembrane segment (TM) of mitochondrial tail–anchored proteins. P5A-ATPase activity mediated the extraction of mistargeted proteins from the endoplasmic reticulum (ER). Cryo–electron microscopy structures of Saccharomyces cerevisiae Spf1 revealed a large, membrane-accessible substrate-binding pocket that alternately faced the ER lumen and cytosol and an endogenous substrate resembling an α-helical TM. Our results indicate that the P5A-ATPase could dislocate misinserted hydrophobic helices flanked by short basic segments from the ER. TM dislocation by the P5A-ATPase establishes an additional class of P-type ATPase substrates and may correct mistakes in protein targeting or topogenesis.

 

DOI:DOI: 10.1126/science.abc5809

 

Source: https://science.sciencemag.org/content/369/6511/eabc5809