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<p>The activation of PLK1 in late G2 is critical for mitotic entry, requiring its phosphorylation by Aurora-A, facilitated by the intrinsically disordered protein Bora. The structural basis of this mechanism has remained unresolved. Here, we present models of the Aurora-A/Bora complex and the Aurora-A/Bora/PLK1 complex, validated with site-specific mutagenesis, biochemical assays and NMR spectroscopy. Bora wraps around the N-lobe of Aurora-A, occupying the pockets used by its other activators. A CDK1 phosphorylation site on Bora (Ser112) mimics the structural role of Aurora-A activation loop phosphorylation within a TPX2-like binding motif. In the ternary complex, Bora bridges the two kinases, orienting the activation loop of PLK1 towards the active site of Aurora-A. Bora residues 56–66 form a critical interface with a conserved pocket on the PLK1 C-helix that is analogous to the TPX2-binding Y-pocket of Aurora-A. Aurora-A phosphorylation of Bora Ser59 creates an additional interaction that increases the efficiency of PLK1 phosphorylation. These findings deepen our understanding of Aurora-A regulation by its disordered binding partners and establish a mechanistic framework for Bora-dependent activation of PLK1.</p>

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Bora bridges Aurora-A activation and substrate recognition of PLK1

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月28日

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  • Jennifer A Miles,
  • Matthew Batchelor,
  • Martin Walko,
  • Vanda Gunning,
  • Andrew J Wilson,
  • Megan H Wright,
  • Richard Bayliss

摘要

The activation of PLK1 in late G2 is critical for mitotic entry, requiring its phosphorylation by Aurora-A, facilitated by the intrinsically disordered protein Bora. The structural basis of this mechanism has remained unresolved. Here, we present models of the Aurora-A/Bora complex and the Aurora-A/Bora/PLK1 complex, validated with site-specific mutagenesis, biochemical assays and NMR spectroscopy. Bora wraps around the N-lobe of Aurora-A, occupying the pockets used by its other activators. A CDK1 phosphorylation site on Bora (Ser112) mimics the structural role of Aurora-A activation loop phosphorylation within a TPX2-like binding motif. In the ternary complex, Bora bridges the two kinases, orienting the activation loop of PLK1 towards the active site of Aurora-A. Bora residues 56–66 form a critical interface with a conserved pocket on the PLK1 C-helix that is analogous to the TPX2-binding Y-pocket of Aurora-A. Aurora-A phosphorylation of Bora Ser59 creates an additional interaction that increases the efficiency of PLK1 phosphorylation. These findings deepen our understanding of Aurora-A regulation by its disordered binding partners and establish a mechanistic framework for Bora-dependent activation of PLK1.