5YI4
Solution Structure of the DISC1/Ndel1 complex
Summary for 5YI4
| Entry DOI | 10.2210/pdb5yi4/pdb |
| NMR Information | BMRB: 36119 |
| Descriptor | Disrupted in schizophrenia 1 homolog,Nuclear distribution protein nudE-like 1 (1 entity in total) |
| Functional Keywords | disc1, ndel1, coiled coil, psychiatric disorder, protein binding |
| Biological source | Mus musculus (Mouse) More |
| Total number of polymer chains | 1 |
| Total formula weight | 15455.42 |
| Authors | |
| Primary citation | Ye, F.,Kang, E.,Yu, C.,Qian, X.,Jacob, F.,Yu, C.,Mao, M.,Poon, R.Y.C.,Kim, J.,Song, H.,Ming, G.L.,Zhang, M. DISC1 Regulates Neurogenesis via Modulating Kinetochore Attachment of Ndel1/Nde1 during Mitosis. Neuron, 96:1041-1054.e5, 2017 Cited by PubMed Abstract: Mutations of DISC1 (disrupted-in-schizophrenia 1) have been associated with major psychiatric disorders. Despite the hundreds of DISC1-binding proteins reported, almost nothing is known about how DISC1 interacts with other proteins structurally to impact human brain development. Here we solved the high-resolution structure of DISC1 C-terminal tail in complex with its binding domain of Ndel1. Mechanistically, DISC1 regulates Ndel1's kinetochore attachment, but not its centrosome localization, during mitosis. Functionally, disrupting DISC1/Ndel1 complex formation prolongs mitotic length and interferes with cell-cycle progression in human cells, and it causes cell-cycle deficits of radial glial cells in the embryonic mouse cortex and human forebrain organoids. We also observed similar deficits in organoids derived from schizophrenia patient induced pluripotent stem cells (iPSCs) with a DISC1 mutation that disrupts its interaction with Ndel1. Our study uncovers a new mechanism of action for DISC1 based on its structure, and it has implications for how genetic insults may contribute to psychiatric disorders. PubMed: 29103808DOI: 10.1016/j.neuron.2017.10.010 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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