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Structure and transport mechanism of P5B-ATPases

Author

Listed:
  • Ping Li

    (Lund University)

  • Kaituo Wang

    (University of Copenhagen)

  • Nina Salustros

    (University of Copenhagen)

  • Christina Grønberg

    (University of Copenhagen)

  • Pontus Gourdon

    (Lund University
    University of Copenhagen)

Abstract

In human cells, P5B-ATPases execute the active export of physiologically important polyamines such as spermine from lysosomes to the cytosol, a function linked to a palette of disorders. Yet, the overall shape of P5B-ATPases and the mechanisms of polyamine recognition, uptake and transport remain elusive. Here we describe a series of cryo-electron microscopy structures of a yeast homolog of human ATP13A2-5, Ypk9, determined at resolutions reaching 3.4 Å, and depicting three separate transport cycle intermediates, including spermine-bound conformations. Surprisingly, in the absence of cargo, Ypk9 rests in a phosphorylated conformation auto-inhibited by the N-terminus. Spermine uptake is accomplished through an electronegative cleft lined by transmembrane segments 2, 4 and 6. Despite the dramatically different nature of the transported cargo, these findings pinpoint shared principles of transport and regulation among the evolutionary related P4-, P5A- and P5B-ATPases. The data also provide a framework for analysis of associated maladies, such as Parkinson’s disease.

Suggested Citation

  • Ping Li & Kaituo Wang & Nina Salustros & Christina Grønberg & Pontus Gourdon, 2021. "Structure and transport mechanism of P5B-ATPases," Nature Communications, Nature, vol. 12(1), pages 1-8, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24148-y
    DOI: 10.1038/s41467-021-24148-y
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    Cited by:

    1. Ping Li & Amber L. Hendricks & Yong Wang & Rhiza Lyne E. Villones & Karin Lindkvist-Petersson & Gabriele Meloni & J. A. Cowan & Kaituo Wang & Pontus Gourdon, 2022. "Structures of Atm1 provide insight into [2Fe-2S] cluster export from mitochondria," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    2. Takuto Fujii & Shushi Nagamori & Pattama Wiriyasermkul & Shizhou Zheng & Asaka Yago & Takahiro Shimizu & Yoshiaki Tabuchi & Tomoyuki Okumura & Tsutomu Fujii & Hiroshi Takeshima & Hideki Sakai, 2023. "Parkinson’s disease-associated ATP13A2/PARK9 functions as a lysosomal H+,K+-ATPase," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    3. Zongxin Guo & Fredrik Orädd & Viktoria Bågenholm & Christina Grønberg & Jian Feng Ma & Peter Ott & Yong Wang & Magnus Andersson & Per Amstrup Pedersen & Kaituo Wang & Pontus Gourdon, 2024. "Diverse roles of the metal binding domains and transport mechanism of copper transporting P-type ATPases," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    4. Jianqiang Mu & Chenyang Xue & Lei Fu & Zongjun Yu & Minhan Nie & Mengqi Wu & Xinmeng Chen & Kun Liu & Ruiqian Bu & Ying Huang & Baisheng Yang & Jianming Han & Qianru Jiang & Kevin C. Chan & Ruhong Zho, 2023. "Conformational cycle of human polyamine transporter ATP13A2," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    5. Ping Li & Viktoria Bågenholm & Per Hägglund & Karin Lindkvist-Petersson & Kaituo Wang & Pontus Gourdon, 2024. "The structure and function of P5A-ATPases," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    6. Wu, Yaobin & Huang, Jiazhou & Chen, Xiangfeng, 2024. "The information value of logistics platforms in a freight matching market," European Journal of Operational Research, Elsevier, vol. 312(1), pages 227-239.

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