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-Structure paper
タイトル | Architecture and structural dynamics of the heteromeric GluK2/K5 kainate receptor. |
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ジャーナル・号・ページ | Elife, Vol. 10, Year 2021 |
掲載日 | 2021年3月16日 |
著者 | Nandish Khanra / Patricia Mge Brown / Amanda M Perozzo / Derek Bowie / Joel R Meyerson / |
PubMed 要旨 | 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. |
リンク | Elife / PubMed:33724189 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 5.3 - 7.5 Å |
構造データ | EMDB-23014, PDB-7ks0: EMDB-23015, PDB-7ks3: EMDB-23017: |
由来 |
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キーワード | SIGNALING PROTEIN / Kainate receptor (カイニン酸型グルタミン酸受容体) / ionotropic glutamate receptor / membrane protein (膜タンパク質) / ligand-gated ion channel (リガンド依存性イオンチャネル) |