4C3P

Structure of dephosphorylated Aurora A (122-403) bound to TPX2 and AMPPCP

4C3P の概要

• エントリーDOI: 10.2210/pdb4c3p/pdb
• 関連するPDBエントリー: 4C3R
• 分子名称: AURORA KINASE A, TARGETING PROTEIN FOR XKLP2, PHOSPHOMETHYLPHOSPHONIC ACID ADENYLATE ESTER, ... (5 entities in total)
• 機能のキーワード: transferase, activation, allostery, cell cycle, cancer
• 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: 76339.62

構造登録者

Zorba, A.,Kutter, S.,Kern, D. (登録日: 2013-08-26, 公開日: 2014-05-28, 最終更新日: 2023-12-20)

主引用文献

Zorba, A.,Buosi, V.,Kutter, S.,Kern, N.,Pontiggia, F.,Cho, Y.J.,Kern, D.
Molecular Mechanism of Aurora a Kinase Autophosphorylation and its Allosteric Activation by Tpx2.
Elife, 3:02667-, 2014

PubMed Abstract: We elucidate the molecular mechanisms of two distinct activation strategies (autophosphorylation and TPX2-mediated activation) in human Aurora A kinase. Classic allosteric activation is in play where either activation loop phosphorylation or TPX2 binding to a conserved hydrophobic groove shifts the equilibrium far towards the active conformation. We resolve the controversy about the mechanism of autophosphorylation by demonstrating intermolecular autophosphorylation in a long-lived dimer by combining X-ray crystallography with functional assays. We then address the allosteric activation by TPX2 through activity assays and the crystal structure of a domain-swapped dimer of dephosphorylated Aurora A and TPX2(1-25). While autophosphorylation is the key regulatory mechanism in the centrosomes in the early stages of mitosis, allosteric activation by TPX2 of dephosphorylated Aurora A could be at play in the spindle microtubules. The mechanistic insights into autophosphorylation and allosteric activation by TPX2 binding proposed here, may have implications for understanding regulation of other protein kinases.DOI: http://dx.doi.org/10.7554/eLife.02667.001.

PubMed: 24867643
DOI: 10.7554/ELIFE.02667

実験手法

X-RAY DIFFRACTION (2.69 Å)