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6VPG

TPX2 residues 7-20 fused to Aurora A residues 116-389 in complex with AMP-PNP

Summary for 6VPG
Entry DOI10.2210/pdb6vpg/pdb
DescriptorTPX2 fragment - Aurora A kinase domain fusion, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, GLYCEROL, ... (6 entities in total)
Functional Keywordsser/thr kinase, transferase
Biological sourceHomo sapiens (Human)
More
Total number of polymer chains1
Total formula weight34760.22
Authors
Lim, D.C.,Yaffe, M.B. (deposition date: 2020-02-03, release date: 2020-08-05, Last modification date: 2024-10-30)
Primary citationLim, D.C.,Joukov, V.,Rettenmaier, T.J.,Kumagai, A.,Dunphy, W.G.,Wells, J.A.,Yaffe, M.B.
Redox priming promotes Aurora A activation during mitosis.
Sci.Signal., 13:-, 2020
Cited by
PubMed Abstract: Cell cycle-dependent redox changes can mediate transient covalent modifications of cysteine thiols to modulate the activities of regulatory kinases and phosphatases. Our previously reported finding that protein cysteine oxidation is increased during mitosis relative to other cell cycle phases suggests that redox modifications could play prominent roles in regulating mitotic processes. The Aurora family of kinases and their downstream targets are key components of the cellular machinery that ensures the proper execution of mitosis and the accurate segregation of chromosomes to daughter cells. In this study, x-ray crystal structures of the Aurora A kinase domain delineate redox-sensitive cysteine residues that, upon covalent modification, can allosterically regulate kinase activity and oligomerization state. We showed in both egg extracts and mammalian cells that a conserved cysteine residue within the Aurora A activation loop is crucial for Aurora A activation by autophosphorylation. We further showed that covalent disulfide adducts of this residue promote autophosphorylation of the Aurora A kinase domain. These findings reveal a potential mechanistic link between Aurora A activation and changes in the intracellular redox state during mitosis and provide insights into how novel small-molecule inhibitors may be developed to target specific subpopulations of Aurora A.
PubMed: 32694171
DOI: 10.1126/scisignal.abb6707
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (2.64 Å)
Structure validation

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