XB-ART-59832
Elife
2023 May 25;12. doi: 10.7554/eLife.85328.
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The structural basis of the multi-step allosteric activation of Aurora B kinase.
Segura-Peña D
,
Hovet O
,
Gogoi H
,
Dawicki-McKenna J
,
Hansen Wøien SM
,
Carrer M
,
Black BE
,
Cascella M
,
Sekulic N
.
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Aurora B, together with IN-box, the C-terminal part of INCENP, forms an enzymatic complex that ensures faithful cell division. The [Aurora B/IN-box] complex is activated by autophosphorylation in the Aurora B activation loop and in IN-box, but it is not clear how these phosphorylations activate the enzyme. We used a combination of experimental and computational studies to investigate the effects of phosphorylation on the molecular dynamics and structure of [Aurora B/IN-box]. In addition, we generated partially phosphorylated intermediates to analyze the contribution of each phosphorylation independently. We found that the dynamics of Aurora and IN-box are interconnected, and IN-box plays both positive and negative regulatory roles depending on the phosphorylation status of the enzyme complex. Phosphorylation in the activation loop of Aurora B occurs intramolecularly and prepares the enzyme complex for activation, but two phosphorylated sites are synergistically responsible for full enzyme activity.
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Genes referenced: incenp
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