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-Structure paper
| タイトル | Cryo-EM structures of higher order Gephyrin oligomers reveal principles of inhibitory postsynaptic scaffold organization. |
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| ジャーナル・号・ページ | Nat Commun, Vol. 17, Issue 1, Year 2026 |
| 掲載日 | 2026年4月16日 |
著者 | Diego Ortiz-López / Tamsanqa T Hove / Christiane Huhn / Serena Camuso / Pia M van Gen Hassend / Bodo Sander / Benjamin F N Campbell / Shiva K Tyagarajan / Andreas Plückthun / Christian G Specht / Hans M Maric / Bettina Böttcher / Hermann Schindelin / ![]() |
| PubMed 要旨 | Gephyrin, the principal scaffolding protein of inhibitory postsynaptic densities, clusters glycine and GABA receptors via multivalent interactions. It features structured N and C terminal domains ...Gephyrin, the principal scaffolding protein of inhibitory postsynaptic densities, clusters glycine and GABA receptors via multivalent interactions. It features structured N and C terminal domains connected by an intrinsically disordered linker. Although the structural and functional properties of its terminal domains are well characterized, the mechanism by which full-length gephyrin organizes into higher-order complexes remains unresolved. Here, we combine biochemical reconstitution, cryo-electron microscopy, and mutational analyses to elucidate the structural logic of gephyrin oligomerization. We demonstrate that gephyrin adopts a stable dimeric assembly which constitutes the basic unit for both linear and oblique tetramers as well as linear hexameric arrangements. High resolution structures reveal a critical segment of the flexible linker that adopts two distinct conformations, one of which occludes the receptor-binding site. This segment harbors key phosphorylation sites, suggesting a regulatory control mechanism. Our findings redefine the architecture of inhibitory postsynaptic sites and reconcile gephyrin oligomerization models with published in-situ postsynaptic densities characterized by cryo-electron tomography. |
リンク | Nat Commun / PubMed:41991925 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 2.31 - 3.48 Å |
| 構造データ | EMDB-54532, PDB-9s3f: ![]() EMDB-54539: Gephyrin E-Domain dimer of dimers - Consensus Map EMDB-54540, PDB-9s3m: ![]() EMDB-54544: Gephyrin E-Domain dimer of dimers - local refinement of dimer A ![]() EMDB-54545: Gephyrin E-Domain dimer of dimers - local refinement of dimer B EMDB-54551, PDB-9s3t: |
| 由来 |
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キーワード | STRUCTURAL PROTEIN / scaffolding protein / postsynaptic density / protein-protein interaction / linker-mediated regulation / STRUCTURAL PROTEIN. |
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