P5-ATPases：结构、底物特异性和运输机制。

P5-ATPases: Structure, substrate specificities, and transport mechanisms.

机构信息

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.

出版信息

Curr Opin Struct Biol. 2023 Apr;79:102531. doi: 10.1016/j.sbi.2023.102531. Epub 2023 Jan 30.

DOI:10.1016/j.sbi.2023.102531

PMID:36724561

Abstract

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.

摘要

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。