2ojx Citations

Molecular and structural basis of polo-like kinase 1 substrate recognition: Implications in centrosomal localization.

Proc Natl Acad Sci U S A 104 3107-12 (2007)
Related entries: 2ogq, 3bzi

Cited: 76 times
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Abstract

Polo-like kinase (Plk1) is crucial for cell cycle progression through mitosis. Here we present the molecular and structural mechanisms that regulate the substrate recognition of Plk1 and influence its centrosomal localization and activity. Our work shows that Plk1 localization is controlled not only by the polo box domain (PBD); remarkably, the kinase domain is also involved in Plk1 targeting mechanism to the centrosome. The crystal structures of the PBD in complex with Cdc25C and Cdc25C-P target peptides reveal that Trp-414 is fundamental in their recognition regardless of its phosphorylation status. Binding measurements demonstrate that W414F mutation abolishes molecular recognition and diminishes centrosomal localization. Therefore, Plk1 centrosomal localization is not controlled by His-538 and Lys-540, the residues involved in phosphorylated target binding. The different conformations of the loop, which connects the polo boxes in the apo and the PBD-Cdc25C and PBD-Cdc25C-P complex structures, together with changes in the proline adjacent to the phosphothreonine in the target peptide, suggest a regulatory mechanism to detect binding of unphosphorylated or phosphorylated target substrates. Altogether, these data propose a model for the interaction between Plk1 and Cdc25C.

Articles - 2ojx mentioned but not cited (4)

  1. Molecular and structural basis of polo-like kinase 1 substrate recognition: Implications in centrosomal localization. García-Alvarez B, de Cárcer G, Ibañez S, Bragado-Nilsson E, Montoya G. Proc Natl Acad Sci U S A 104 3107-3112 (2007)
  2. Computational analysis of phosphopeptide binding to the polo-box domain of the mitotic kinase PLK1 using molecular dynamics simulation. Huggins DJ, McKenzie GJ, Robinson DD, Narváez AJ, Hardwick B, Roberts-Thomson M, Venkitaraman AR, Grant GH, Payne MC. PLoS Comput Biol 6 e1000880 (2010)
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  4. Structure of the Brachydanio rerio Polo-like kinase 1 (Plk1) catalytic domain in complex with an extended inhibitor targeting the adaptive pocket of the enzyme. Elling RA, Fucini RV, Hanan EJ, Barr KJ, Zhu J, Paulvannan K, Yang W, Romanowski MJ. Acta Crystallogr Sect F Struct Biol Cryst Commun 64 686-691 (2008)


Reviews citing this publication (20)

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Articles citing this publication (52)

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