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Structure of a glutamate transporter homologue from Pyrococcus horikoshii

Author

Listed:
  • Dinesh Yernool

    (Columbia University)

  • Olga Boudker

    (Columbia University
    Columbia University)

  • Yan Jin

    (Columbia University)

  • Eric Gouaux

    (Columbia University
    Columbia University)

Abstract

Glutamate transporters are integral membrane proteins that catalyse the concentrative uptake of glutamate from the synapse to intracellular spaces by harnessing pre-existing ion gradients. In the central nervous system glutamate transporters are essential for normal development and function, and are implicated in stroke, epilepsy and neurodegenerative diseases. Here we present the crystal structure of a eukaryotic glutamate transporter homologue from Pyrococcus horikoshii. The transporter is a bowl-shaped trimer with a solvent-filled extracellular basin extending halfway across the membrane bilayer. At the bottom of the basin are three independent binding sites, each cradled by two helical hairpins, reaching from opposite sides of the membrane. We propose that transport of glutamate is achieved by movements of the hairpins that allow alternating access to either side of the membrane.

Suggested Citation

  • Dinesh Yernool & Olga Boudker & Yan Jin & Eric Gouaux, 2004. "Structure of a glutamate transporter homologue from Pyrococcus horikoshii," Nature, Nature, vol. 431(7010), pages 811-818, October.
  • Handle: RePEc:nat:nature:v:431:y:2004:i:7010:d:10.1038_nature03018
    DOI: 10.1038/nature03018
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    Cited by:

    1. 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.
    2. 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.
    3. 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.
    4. 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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