5YI4

Solution Structure of the DISC1/Ndel1 complex

5YI4 の概要

• エントリーDOI: 10.2210/pdb5yi4/pdb
• NMR情報: BMRB: 36119
• 分子名称: Disrupted in schizophrenia 1 homolog,Nuclear distribution protein nudE-like 1 (1 entity in total)
• 機能のキーワード: disc1, ndel1, coiled coil, psychiatric disorder, protein binding
• 由来する生物種: Mus musculus (Mouse); 詳細
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 15455.42

構造登録者

Ye, F.,Yu, C.,Yu, C.,Zhang, M. (登録日: 2017-10-02, 公開日: 2017-11-15, 最終更新日: 2024-05-15)

主引用文献

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

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: 29103808
DOI: 10.1016/j.neuron.2017.10.010

実験手法

SOLUTION NMR