9S3T
Gephyrin dimer of dimers - combined CryoEM map
Summary for 9S3T
| Entry DOI | 10.2210/pdb9s3t/pdb |
| EMDB information | 54551 |
| Descriptor | Isoform 5 of Gephyrin (1 entity in total) |
| Functional Keywords | scaffolding protein, postsynaptic density, protein-protein interaction, linker-mediated regulation, structural protein |
| Biological source | Rattus norvegicus (Norway rat) |
| Total number of polymer chains | 4 |
| Total formula weight | 326892.97 |
| Authors | Ortiz-Lopez, D.,Hove, T.,Boettcher, B.,Schindelin, H. (deposition date: 2025-07-25, release date: 2026-06-24) |
| Primary citation | Ortiz-Lopez, D.,Hove, T.T.,Huhn, C.,Camuso, S.,van Gen Hassend, P.M.,Sander, B.,Campbell, B.F.N.,Tyagarajan, S.K.,Pluckthun, A.,Specht, C.G.,Maric, H.M.,Bottcher, B.,Schindelin, H. Cryo-EM structures of higher order Gephyrin oligomers reveal principles of inhibitory postsynaptic scaffold organization. Nat Commun, 17:-, 2026 Cited by PubMed Abstract: 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. PubMed: 41991925DOI: 10.1038/s41467-026-71771-8 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.48 Å) |
Structure validation
Download full validation report
