Cryo-EM structures and transport mechanism of human P5B type ATPase ATP13A2

Abstract Polyamines are important polycations that play critical roles in mammalian cells. ATP13A2 belongs to the orphan P5B adenosine triphosphatases (ATPase) family and has been established as a lysosomal polyamine exporter to maintain the normal function of lysosomes and mitochondria. Previous st...

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Autores principales:	Xudong Chen, Mingze Zhou, Sensen Zhang, Jian Yin, Ping Zhang, Xujun Xuan, Peiyi Wang, Zhiqiang Liu, Boda Zhou, Maojun Yang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Publishing Group 2021
Materias:	Cytology QH573-671
Acceso en línea:	https://doaj.org/article/3f5298797b4f46a199443c8307955b66
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spelling	oai:doaj.org-article:3f5298797b4f46a199443c8307955b662021-11-08T11:14:38ZCryo-EM structures and transport mechanism of human P5B type ATPase ATP13A210.1038/s41421-021-00334-62056-5968https://doaj.org/article/3f5298797b4f46a199443c8307955b662021-11-01T00:00:00Zhttps://doi.org/10.1038/s41421-021-00334-6https://doaj.org/toc/2056-5968Abstract Polyamines are important polycations that play critical roles in mammalian cells. ATP13A2 belongs to the orphan P5B adenosine triphosphatases (ATPase) family and has been established as a lysosomal polyamine exporter to maintain the normal function of lysosomes and mitochondria. Previous studies have reported that several human neurodegenerative disorders are related to mutations in the ATP13A2 gene. However, the transport mechanism of ATP13A2 in the lysosome remains unclear. Here, we report the cryo-electron microscopy (cryo-EM) structures of three distinct intermediates of the human ATP13A2, revealing key insights into the spermine (SPM) transport cycle in the lysosome. The transmembrane domain serves as a substrate binding site and the C-terminal domain is essential for protein stability and may play a regulatory role. These findings advance our understanding of the polyamine transport mechanism, the lipid-associated regulation, and the disease-associated mutants of ATP13A2.Xudong ChenMingze ZhouSensen ZhangJian YinPing ZhangXujun XuanPeiyi WangZhiqiang LiuBoda ZhouMaojun YangNature Publishing GrouparticleCytologyQH573-671ENCell Discovery, Vol 7, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Cytology QH573-671
spellingShingle	Cytology QH573-671 Xudong Chen Mingze Zhou Sensen Zhang Jian Yin Ping Zhang Xujun Xuan Peiyi Wang Zhiqiang Liu Boda Zhou Maojun Yang Cryo-EM structures and transport mechanism of human P5B type ATPase ATP13A2
description	Abstract Polyamines are important polycations that play critical roles in mammalian cells. ATP13A2 belongs to the orphan P5B adenosine triphosphatases (ATPase) family and has been established as a lysosomal polyamine exporter to maintain the normal function of lysosomes and mitochondria. Previous studies have reported that several human neurodegenerative disorders are related to mutations in the ATP13A2 gene. However, the transport mechanism of ATP13A2 in the lysosome remains unclear. Here, we report the cryo-electron microscopy (cryo-EM) structures of three distinct intermediates of the human ATP13A2, revealing key insights into the spermine (SPM) transport cycle in the lysosome. The transmembrane domain serves as a substrate binding site and the C-terminal domain is essential for protein stability and may play a regulatory role. These findings advance our understanding of the polyamine transport mechanism, the lipid-associated regulation, and the disease-associated mutants of ATP13A2.
format	article
author	Xudong Chen Mingze Zhou Sensen Zhang Jian Yin Ping Zhang Xujun Xuan Peiyi Wang Zhiqiang Liu Boda Zhou Maojun Yang
author_facet	Xudong Chen Mingze Zhou Sensen Zhang Jian Yin Ping Zhang Xujun Xuan Peiyi Wang Zhiqiang Liu Boda Zhou Maojun Yang
author_sort	Xudong Chen
title	Cryo-EM structures and transport mechanism of human P5B type ATPase ATP13A2
title_short	Cryo-EM structures and transport mechanism of human P5B type ATPase ATP13A2
title_full	Cryo-EM structures and transport mechanism of human P5B type ATPase ATP13A2
title_fullStr	Cryo-EM structures and transport mechanism of human P5B type ATPase ATP13A2
title_full_unstemmed	Cryo-EM structures and transport mechanism of human P5B type ATPase ATP13A2
title_sort	cryo-em structures and transport mechanism of human p5b type atpase atp13a2
publisher	Nature Publishing Group
publishDate	2021
url	https://doaj.org/article/3f5298797b4f46a199443c8307955b66
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Cryo-EM structures and transport mechanism of human P5B type ATPase ATP13A2

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