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Structure paper

TitleKainate receptor modulation by NETO2.
Journal, issue, pagesNature, Vol. 599, Issue 7884, Page 325-329, Year 2021
Publish dateSep 22, 2021
AuthorsLingli 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 /
PubMed AbstractGlutamate-gated kainate receptors are ubiquitous in the central nervous system of vertebrates, mediate synaptic transmission at the postsynapse and modulate transmitter release at the presynapse. In ...Glutamate-gated kainate receptors are ubiquitous in the central nervous system of vertebrates, mediate synaptic transmission at the postsynapse and modulate transmitter release at the presynapse. In the brain, the trafficking, gating kinetics and pharmacology of kainate receptors are tightly regulated by neuropilin and tolloid-like (NETO) proteins. Here we report cryo-electron microscopy structures of homotetrameric GluK2 in complex with NETO2 at inhibited and desensitized states, illustrating variable stoichiometry of GluK2-NETO2 complexes, with one or two NETO2 subunits associating with GluK2. We find that NETO2 accesses only two broad faces of kainate receptors, intermolecularly crosslinking the lower lobe of ATD, the upper lobe of LBD and the lower lobe of LBD, 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 interaction with an intracellular cap domain formed by the M1-M2 linkers of the receptor, revealing how rectification is regulated by NETO2.
External linksNature / PubMed:34552241
MethodsEM (single particle)
Resolution3.8 - 6.4 Å
Structure data

EMDB-31459, PDB-7f56:
DNQX-bound GluK2-1xNeto2 complex, with asymmetric LBD
Method: EM (single particle) / Resolution: 4.1 Å

EMDB-31460, PDB-7f57:
Kainate-bound GluK2-1xNeto2 complex, at the desensitized state
Method: EM (single particle) / Resolution: 3.8 Å

EMDB-31462, PDB-7f59:
DNQX-bound GluK2-1xNeto2 complex
Method: EM (single particle) / Resolution: 4.2 Å

EMDB-31463, PDB-7f5a:
DNQX-bound GluK2-2xNeto2 complex
Method: EM (single particle) / Resolution: 6.4 Å

EMDB-31464, PDB-7f5b:
LBD-TMD focused reconstruction of DNQX-bound GluK2-1xNeto2 complex
Method: EM (single particle) / Resolution: 3.9 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

ChemComp-PGT:
(1S)-2-{[{[(2R)-2,3-DIHYDROXYPROPYL]OXY}(HYDROXY)PHOSPHORYL]OXY}-1-[(PALMITOYLOXY)METHYL]ETHYL STEARATE / phospholipid*YM

ChemComp-CA:
Unknown entry

Source
  • rattus norvegicus (Norway rat)
KeywordsMEMBRANE PROTEIN / Ionotropic glutamate receptors / Single-pass transmembrane proteins

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