8PR7

Aurora-A in complex with CEP192 and an inhibitory monobody

8PR7 の概要

• エントリーDOI: 10.2210/pdb8pr7/pdb
• 分子名称: Aurora kinase A, Monobody, Centrosomal protein of 192 kDa, ... (7 entities in total)
• 機能のキーワード: kinase, inhibitor, allosteric, disordered, phosphorylation, transferase
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 102491.40

構造登録者

Miles, J.A.,Bayliss, R. (登録日: 2023-07-12, 公開日: 2024-07-24, 最終更新日: 2025-02-05)

主引用文献

Holder, J.,Miles, J.A.,Batchelor, M.,Popple, H.,Walko, M.,Yeung, W.,Kannan, N.,Wilson, A.J.,Bayliss, R.,Gergely, F.
CEP192 localises mitotic Aurora-A activity by priming its interaction with TPX2.
Embo J., 43:5381-5420, 2024

PubMed Abstract: Aurora-A is an essential cell-cycle kinase with critical roles in mitotic entry and spindle dynamics. These functions require binding partners such as CEP192 and TPX2, which modulate both kinase activity and localisation of Aurora-A. Here we investigate the structure and role of the centrosomal Aurora-A:CEP192 complex in the wider molecular network. We find that CEP192 wraps around Aurora-A, occupies the binding sites for mitotic spindle-associated partners, and thus competes with them. Comparison of two different Aurora-A conformations reveals how CEP192 modifies kinase activity through the site used for TPX2-mediated activation. Deleting the Aurora-A-binding interface in CEP192 prevents centrosomal accumulation of Aurora-A, curtails its activation-loop phosphorylation, and reduces spindle-bound TPX2:Aurora-A complexes, resulting in error-prone mitosis. Thus, by supplying the pool of phosphorylated Aurora-A necessary for TPX2 binding, CEP192:Aurora-A complexes regulate spindle function. We propose an evolutionarily conserved spatial hierarchy, which protects genome integrity through fine-tuning and correctly localising Aurora-A activity.

PubMed: 39327527
DOI: 10.1038/s44318-024-00240-z

実験手法

X-RAY DIFFRACTION (2.76 Å)