7f59

DNQX-bound GluK2-1xNeto2 complexDNQX-bound GluK2-1xNeto2 complex

Structural highlights

7f59 is a 5 chain structure with sequence from Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 4.2Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

NETO2_RAT

Publication Abstract from PubMed

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(1-7). In the brain, the trafficking, gating kinetics and pharmacology of kainate receptors are tightly regulated by neuropilin and tolloid-like (NETO) proteins(8-11). 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(A/C), the upper lobe of LBD(B/D) and the lower lobe of LBD(A/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 interaction with an intracellular cap domain formed by the M1-M2 linkers of the receptor, revealing how rectification is regulated by NETO2.

Kainate receptor modulation by NETO2.,He L, Sun J, Gao Y, Li B, Wang Y, Dong Y, An W, Li H, Yang B, Ge Y, Zhang XC, Shi YS, Zhao Y Nature. 2021 Nov;599(7884):325-329. doi: 10.1038/s41586-021-03936-y. Epub 2021 , Sep 22. PMID:34552241^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ He L, Sun J, Gao Y, Li B, Wang Y, Dong Y, An W, Li H, Yang B, Ge Y, Zhang XC, Shi YS, Zhao Y. Kainate receptor modulation by NETO2. Nature. 2021 Nov;599(7884):325-329. PMID:34552241 doi:10.1038/s41586-021-03936-y

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] He L, Sun J, Gao Y, Li B, Wang Y, Dong Y, An W, Li H, Yang B, Ge Y, Zhang XC, Shi YS, Zhao Y. Kainate receptor modulation by NETO2. Nature. 2021 Nov;599(7884):325-329. PMID:34552241 doi:10.1038/s41586-021-03936-y

[1]