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Chen X, Zhou M, Zhang S, et al. Cryo-EM structures and transport mechanism of human P5B type ATPase ATP13A2. Cell Discov. 2021;7(1):106doi: 10.1038/s41421-021-00334-6.
Chen, X., Zhou, M., Zhang, S., Yin, J., Zhang, P., Xuan, X., Wang, P., Liu, Z., Zhou, B., & Yang, M. (2021). Cryo-EM structures and transport mechanism of human P5B type ATPase ATP13A2. Cell discovery, 7(1), 106. https://doi.org/10.1038/s41421-021-00334-6
Chen, Xudong, et al. "Cryo-EM structures and transport mechanism of human P5B type ATPase ATP13A2." Cell discovery vol. 7,1 (2021): 106. doi: https://doi.org/10.1038/s41421-021-00334-6
Chen X, Zhou M, Zhang S, Yin J, Zhang P, Xuan X, Wang P, Liu Z, Zhou B, Yang M. Cryo-EM structures and transport mechanism of human P5B type ATPase ATP13A2. Cell Discov. 2021 Nov 02;7(1):106. doi: 10.1038/s41421-021-00334-6. PMID: 34728622; PMCID: PMC8564547.
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Cell Discov. 2021 Nov 02;7(1):106. doi: 10.1038/s41421-021-00334-6.

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

Cell discovery

Xudong Chen, Mingze Zhou, Sensen Zhang, Jian Yin, Ping Zhang, Xujun Xuan, Peiyi Wang, Zhiqiang Liu, Boda Zhou, Maojun Yang

Affiliations

  1. Ministry of Education Key Laboratory of Protein Science, Tsinghua-Peking Center for Life Sciences, Beijing Advanced Innovation Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing, China.
  2. Department of Cardiology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China.
  3. Department of Andrology, The Seventh Affiliated Hospital, Sun Yat-sen University, ShenZhen, Guangdong, China.
  4. Cryo-EM Facility Center, Southern University of Science & Technology, Shenzhen, Guangdong, China. [email protected].
  5. Department of Anesthesiology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China. [email protected].
  6. Department of Cardiology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China. [email protected].
  7. Ministry of Education Key Laboratory of Protein Science, Tsinghua-Peking Center for Life Sciences, Beijing Advanced Innovation Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing, China. [email protected].
  8. Cryo-EM Facility Center, Southern University of Science & Technology, Shenzhen, Guangdong, China. [email protected].

PMID: 34728622 PMCID: PMC8564547 DOI: 10.1038/s41421-021-00334-6

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.

© 2021. The Author(s).

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