9RUX
Cryo-EM structure of DISC1 core
Summary for 9RUX
| Entry DOI | 10.2210/pdb9rux/pdb |
| EMDB information | 54277 |
| Descriptor | Disrupted in schizophrenia 1 homolog (1 entity in total) |
| Functional Keywords | scaffold, complex, tetramer, coiled coil, uvr domain, psychiatric disorder, structural protein |
| Biological source | Mus musculus (house mouse) |
| Total number of polymer chains | 4 |
| Total formula weight | 215359.66 |
| Authors | |
| Primary citation | Zhou, J.C.,Kratochvil, J.,Ye, F.,El Omari, K.,Kukura, P.,Zhang, M.,Seiradake, E. The schizophrenia associated protein DISC1 forms a multivalent tetrameric hub via conserved UVR dimers. Nat Commun, 2026 Cited by PubMed Abstract: DISC1 is a pleiotropic protein with essential roles in neuronal proliferation and migration, intracellular signalling and cargo transport. It associates with a diverse array of partner molecules in these contexts. Mutations at the DISC1 locus are strongly associated with a spectrum of mental illnesses such as schizophrenia and depression. Despite its clinical relevance, the molecular architecture and function of DISC1 have remained largely elusive. We present a cryo-EM structure of the entire conserved core region of DISC1. The structure reveals an intricate homotetrameric assembly that harbours conserved bacteria-derived UVR domains. Four of these domains, one from each monomer, mediate extensive contacts forming two asymmetric dimer units. The dimers in turn interface with each other at two distinct coiled coil domains to achieve a two-fold symmetric tetramer. Mutational analysis shows that this tetrameric architecture enables DISC1 to simultaneously bind multiple copies of NDE1 client protein. Importantly, tetramerization and partner binding are structurally independent functions of DISC1. Altogether, our study provides a compelling molecular model of an ancient bacteria protein fold participating in the assembly of a multivalent mammalian scaffold hub that can coordinate multiple partner molecules. PubMed: 41997921DOI: 10.1038/s41467-026-71838-6 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.9 Å) |
Structure validation
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