Kainate receptor modulation by NETO2
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.
Cite
@article{arxiv.2302.00887,
title = {Kainate receptor modulation by NETO2},
author = {Lingli He and Jiahui Sun and Yiwei Gao and Bin Li and Yuhang Wang and Yanli Dong and Weidong An and Hang Li and Bei Yang and Yuhan Ge and Xuejun Cai Zhang and Yun Stone Shi and Yan Zhao},
journal= {arXiv preprint arXiv:2302.00887},
year = {2023}
}