Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA; California Institute for Quantitative Biosciences, University of California, Berkeley, CA 94720, USA.
Curr Opin Struct Biol. 2023 Apr;79:102531. doi: 10.1016/j.sbi.2023.102531. Epub 2023 Jan 30.
P5A- and P5B- ATPases, or collectively P5-ATPases, are eukaryotic-specific ATP-dependent transporters that are important for the function of the endoplasmic reticulum (ER) and endo-/lysosomes. However, their substrate specificities had remained enigmatic for many years. Recent cryo-electron microscopy (cryo-EM) and biochemical studies of P5-ATPases have revealed their substrate specificities and transport mechanisms, which were found to be markedly different from other members of the P-type ATPase superfamily. The P5A-ATPase extracts mistargeted or mis-inserted transmembrane helices from the ER membrane for protein quality control, while the P5B-ATPases mediate export of polyamines from late endo-/lysosomes into the cytosol. In this review, we discuss the mechanisms of their substrate recognition and transport based on the cryo-EM structures of the yeast and human P5-ATPases. We highlight how structural diversification of the transmembrane domain has enabled the P5-ATPase subfamily to adapt for transport of atypical substrates.
P5A- 和 P5B-ATP 酶，或统称为 P5-ATP 酶，是真核生物特有的 ATP 依赖性转运蛋白，对于内质网 (ER) 和内体/溶酶体的功能至关重要。然而，多年来，它们的底物特异性一直是个谜。最近的冷冻电子显微镜 (cryo-EM) 和 P5-ATP 酶的生化研究揭示了它们的底物特异性和运输机制，这些机制与 P 型 ATP 酶超家族的其他成员明显不同。P5A-ATP 酶从 ER 膜中提取靶向错误或插入错误的跨膜螺旋，以进行蛋白质质量控制，而 P5B-ATP 酶介导多胺从晚期内体/溶酶体向细胞质的输出。在这篇综述中，我们根据酵母和人类 P5-ATP 酶的 cryo-EM 结构讨论了它们的底物识别和运输机制。我们强调了跨膜结构域的结构多样化如何使 P5-ATP 酶亚家族能够适应运输非典型底物。
