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The structural basis of the multi-step allosteric activation of Aurora B kinase

ABSTRACT: 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.

INSTRUMENT(S): Synapt MS

ORGANISM(S): Xenopus Cf. Laevis Uf 185698

SUBMITTER: Dario Segura-Pena

LAB HEAD: Nikolina Sekulic

PROVIDER: PXD038935 | Pride | 2023-05-31

REPOSITORIES: Pride

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