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-Structure paper
| タイトル | Human GlyRα2 pore dynamics in gating and inhibition. |
|---|---|
| ジャーナル・号・ページ | Structure, Year 2026 |
| 掲載日 | 2026年3月18日 |
著者 | Emily Klemm / Eric Gibbs / Madeleine Stauffer / Devesh Mohapatra / Chloe Meyer / Sudha Chakrapani / ![]() |
| PubMed 要旨 | Glycine receptors (GlyRs) mediate inhibitory neurotransmission in the central nervous system. The GlyRα2 subtype contributes to critical neural circuitry in early neurodevelopment and is also found ...Glycine receptors (GlyRs) mediate inhibitory neurotransmission in the central nervous system. The GlyRα2 subtype contributes to critical neural circuitry in early neurodevelopment and is also found in adults. GlyRα2 dysfunctions are implicated in neurodevelopmental disorders, including autism, epilepsy, and cognitive delays. GlyRα2 functional properties and pharmacology are distinct from GlyRα1, but the structural basis for these differences remains poorly defined. Here, we report cryo-electron microscopy structures of full-length, human GlyRα2 reconstituted in peptidiscs captured in multiple conformational states. In addition to symmetric resting and desensitized states, we resolved an asymmetric open state, previously observed only in heteromeric GlyRs. This suggests that asymmetry is intrinsic to GlyRα2, independent of β-subunit incorporation. Furthermore, we identified distinct conformations of GlyRα2 with the pore-blocker picrotoxin, providing new insights into allosteric interactions. These findings uncover the structural basis of GlyRα2 function, providing a foundation for understanding its role in development and in GlyRα2-associated disorders. |
リンク | Structure / PubMed:41856109 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 2.5 - 3.6 Å |
| 構造データ | EMDB-72665, PDB-9y7p: EMDB-72668, PDB-9y7w: EMDB-72674, PDB-9y7x: EMDB-72675, PDB-9y7z: EMDB-72676, PDB-9y80: EMDB-72683, PDB-9y8z: EMDB-72688, PDB-9y94: EMDB-72689, PDB-9y95: EMDB-72690, PDB-9y96: |
| 化合物 | ![]() ChemComp-NAG: ![]() ChemComp-GLY: ![]() ChemComp-PX4: ![]() ChemComp-RI5: ![]() ChemComp-CLR: |
| 由来 |
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キーワード | TRANSPORT PROTEIN / homopentamer / ion channel / ligand gated ion channel |
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homo sapiens (ヒト)
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