7B1F

Orthorhombic P212121 Structure of Human Mad1 C-terminal Domain in Complex with Phosphorylated Bub1 CD1 Domain

7B1F の概要

• エントリーDOI: 10.2210/pdb7b1f/pdb
• 分子名称: Mitotic spindle assembly checkpoint protein MAD1, Mitotic checkpoint serine/threonine-protein kinase BUB1 (3 entities in total)
• 機能のキーワード: mad1, bub1, mitotic checkpoint complex, spindle assembly checkpoint, cell cycle
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 33970.24

構造登録者

Fischer, E.,Bellini, D.,Barford, D. (登録日: 2020-11-24, 公開日: 2021-03-17, 最終更新日: 2024-01-31)

主引用文献

Fischer, E.S.,Yu, C.W.H.,Bellini, D.,McLaughlin, S.H.,Orr, C.M.,Wagner, A.,Freund, S.M.V.,Barford, D.
Molecular mechanism of Mad1 kinetochore targeting by phosphorylated Bub1.
Embo Rep., 22:e52242-e52242, 2021

PubMed Abstract: During metaphase, in response to improper kinetochore-microtubule attachments, the spindle assembly checkpoint (SAC) activates the mitotic checkpoint complex (MCC), an inhibitor of the anaphase-promoting complex/cyclosome (APC/C). This process is orchestrated by the kinase Mps1, which initiates the assembly of the MCC onto kinetochores through a sequential phosphorylation-dependent signalling cascade. The Mad1-Mad2 complex, which is required to catalyse MCC formation, is targeted to kinetochores through a direct interaction with the phosphorylated conserved domain 1 (CD1) of Bub1. Here, we present the crystal structure of the C-terminal domain of Mad1 (Mad1 ) bound to two phosphorylated Bub1 peptides at 1.75 Å resolution. This interaction is mediated by phosphorylated Bub1 Thr461, which not only directly interacts with Arg617 of the Mad1 RLK (Arg-Leu-Lys) motif, but also directly acts as an N-terminal cap to the CD1 α-helix dipole. Surprisingly, only one Bub1 peptide binds to the Mad1 homodimer in solution. We suggest that this stoichiometry is due to inherent asymmetry in the coiled-coil of Mad1 and has implications for how the Mad1-Bub1 complex at kinetochores promotes efficient MCC assembly.

PubMed: 34013668
DOI: 10.15252/embr.202052242

実験手法

X-RAY DIFFRACTION (1.75 Å)