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Structural ensemble of a glutamate transporter homologue in lipid nanodisc environment

Author

Listed:
  • Valentina Arkhipova

    (University of Groningen)

  • Albert Guskov

    (University of Groningen
    Moscow Institute of Physics and Technology)

  • Dirk J. Slotboom

    (University of Groningen
    University of Groningen)

Abstract

Glutamate transporters are cation-coupled secondary active membrane transporters that clear the neurotransmitter L-glutamate from the synaptic cleft. These transporters are homotrimers, with each protomer functioning independently by an elevator-type mechanism, in which a mobile transport domain alternates between inward- and outward-oriented states. Using single-particle cryo-EM we have determined five structures of the glutamate transporter homologue GltTk, a Na+- L-aspartate symporter, embedded in lipid nanodiscs. Dependent on the substrate concentrations used, the protomers of the trimer adopt a variety of asymmetrical conformations, consistent with the independent movement. Six of the 15 resolved protomers are in a hitherto elusive state of the transport cycle in which the inward-facing transporters are loaded with Na+ ions. These structures explain how substrate-leakage is prevented – a strict requirement for coupled transport. The belt protein of the lipid nanodiscs bends around the inward oriented protomers, suggesting that membrane deformations occur during transport.

Suggested Citation

  • Valentina Arkhipova & Albert Guskov & Dirk J. Slotboom, 2020. "Structural ensemble of a glutamate transporter homologue in lipid nanodisc environment," Nature Communications, Nature, vol. 11(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-14834-8
    DOI: 10.1038/s41467-020-14834-8
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    Cited by:

    1. Biao Qiu & Olga Boudker, 2023. "Symport and antiport mechanisms of human glutamate transporters," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    2. Takafumi Kato & Tsukasa Kusakizako & Chunhuan Jin & Xinyu Zhou & Ryuichi Ohgaki & LiLi Quan & Minhui Xu & Suguru Okuda & Kan Kobayashi & Keitaro Yamashita & Tomohiro Nishizawa & Yoshikatsu Kanai & Osa, 2022. "Structural insights into inhibitory mechanism of human excitatory amino acid transporter EAAT2," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    3. Chancievan Thangaratnarajah & Mark Nijland & Luís Borges-Araújo & Aike Jeucken & Jan Rheinberger & Siewert J. Marrink & Paulo C. T. Souza & Cristina Paulino & Dirk J. Slotboom, 2023. "Expulsion mechanism of the substrate-translocating subunit in ECF transporters," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    4. Emanuela Colucci & Zaid R. Anshari & Miyer F. Patiño-Ruiz & Mariia Nemchinova & Jacob Whittaker & Dirk J. Slotboom & Albert Guskov, 2023. "Mutation in glutamate transporter homologue GltTk provides insights into pathologic mechanism of episodic ataxia 6," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    5. Zhenglai Zhang & Huiwen Chen & Ze Geng & Zhuoya Yu & Hang Li & Yanli Dong & Hongwei Zhang & Zhuo Huang & Juquan Jiang & Yan Zhao, 2022. "Structural basis of ligand binding modes of human EAAT2," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    6. Anna M. Borowska & Maria Gabriella Chiariello & Alisa A. Garaeva & Jan Rheinberger & Siewert J. Marrink & Cristina Paulino & Dirk J. Slotboom, 2024. "Structural basis of the obligatory exchange mode of human neutral amino acid transporter ASCT2," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    7. David B. Sauer & Jennifer J. Marden & Joseph C. Sudar & Jinmei Song & Christopher Mulligan & Da-Neng Wang, 2022. "Structural basis of ion – substrate coupling in the Na+-dependent dicarboxylate transporter VcINDY," Nature Communications, Nature, vol. 13(1), pages 1-9, December.

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