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Quantitative Biology > Biomolecules

arXiv:2302.00887 (q-bio)
[Submitted on 2 Feb 2023]

Title:Kainate receptor modulation by NETO2

Authors:Lingli He, Jiahui Sun, Yiwei Gao, Bin Li, Yuhang Wang, Yanli Dong, Weidong An, Hang Li, Bei Yang, Yuhan Ge, Xuejun Cai Zhang, Yun Stone Shi, Yan Zhao
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Abstract:Glutamate-gated kainate receptors (KARs) are ubiquitous in the central nervous system of vertebrates, mediate synaptic transmission on post-synapse, and modulate transmitter release on pre-synapse. In the brain, the trafficking, gating kinetics, and pharmacology of KARs are tightly regulated by Neuropilin and tolloid-like proteins (Netos). Here we report cryo-EM structures of homo-tetrameric GluK2 in complex with Neto2 at inhibited and desensitized states, illustrating variable stoichiometry of GluK2-Neto2 complexes, with one or two Neto2 subunits associate with the GluK2. We find that Neto2 accesses only two broad faces of KARs, intermolecularly crosslinking the lower-lobe of ATDA/C, upper-lobe of LBDB/D, and lower-lobe of LBDA/C, illustrating how Neto2 regulates receptor-gating kinetics. The transmembrane helix of Neto2 is positioned proximal to the selectivity filter and competes with the amphiphilic H1-helix after M4 for interacting with an ICD formed by the M1-M2 linkers of the receptor, revealing how rectification is regulated by Neto2.
Subjects: Biomolecules (q-bio.BM)
Cite as: arXiv:2302.00887 [q-bio.BM]
  (or arXiv:2302.00887v1 [q-bio.BM] for this version)
  https://doi.org/10.48550/arXiv.2302.00887
Journal reference: Nature, 599(7884), 325-329 (2021)
Related DOI: https://doi.org/10.1038/s41586-021-03936-y

Submission history

From: Yiwei Gao [view email]
[v1] Thu, 2 Feb 2023 05:36:51 UTC (17,617 KB)
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