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| Title | Architecture and structural dynamics of the heteromeric GluK2/K5 kainate receptor. |
|---|---|
| Journal, issue, pages | Elife, Vol. 10, Year 2021 |
| Publish date | Mar 16, 2021 |
 Authors | Nandish Khanra / Patricia Mge Brown / Amanda M Perozzo / Derek Bowie / Joel R Meyerson /   |
| PubMed Abstract | Kainate receptors (KARs) are L-glutamate-gated ion channels that regulate synaptic transmission and modulate neuronal circuits. KARs have strict assembly rules and primarily function as heteromeric ...Kainate receptors (KARs) are L-glutamate-gated ion channels that regulate synaptic transmission and modulate neuronal circuits. KARs have strict assembly rules and primarily function as heteromeric receptors in the brain. A longstanding question is how KAR heteromer subunits organize and coordinate together to fulfill their signature physiological roles. Here we report structures of the GluK2/GluK5 heteromer in apo, antagonist-bound, and desensitized states. The receptor assembles with two copies of each subunit, ligand binding domains arranged as two heterodimers and GluK5 subunits proximal to the channel. Strikingly, during desensitization, GluK2, but not GluK5, subunits undergo major structural rearrangements to facilitate channel closure. We show how the large conformational differences between antagonist-bound and desensitized states are mediated by the linkers connecting the pore helices to the ligand binding domains. This work presents the first KAR heteromer structure, reveals how its subunits are organized, and resolves how the heteromer can accommodate functionally distinct closed channel structures. |
 External links | Elife / PubMed:33724189 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 5.3 - 7.5 Å |
| Structure data | EMDB-23014, PDB-7ks0: EMDB-23015, PDB-7ks3:  EMDB-23017: |
| Source |
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 Keywords | SIGNALING PROTEIN / Kainate receptor / ionotropic glutamate receptor / membrane protein / ligand-gated ion channel |
rattus norvegicus (Norway rat)
aequorea victoria (jellyfish)