The structure of C290A:C393A Aurora A provides structural insights into kinase regulation

Acta Crystallogr F Struct Biol Commun. 2015 Mar;71(Pt 3):315-9. doi: 10.1107/S2053230X15002290. Epub 2015 Feb 19.

Abstract

Aurora A is a Ser/Thr protein kinase that functions in cell-cycle regulation and is implicated in cancer development. During mitosis, Aurora A is activated by autophosphorylation on its activation loop at Thr288. The Aurora A catalytic domain (amino acids 122-403) expressed in Escherichia coli autophosphorylates on two activation-loop threonine residues (Thr288 and Thr287), whereas a C290A,C393A double point mutant of the Aurora A catalytic domain autophosphorylates only on Thr288. The structure of the complex of this mutant with ADP and magnesium was determined to 2.1 Å resolution using molecular replacement. This is an improvement on the existing 2.75 Å resolution structure of the equivalent wild-type complex. The structure confirms that single phosphorylation of the activation loop on Thr288 is insufficient to stabilize a `fully active' conformation of the activation loop in the absence of binding to TPX2.

Keywords: activation; phosphorylation; protein kinase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aurora Kinase A / chemistry*
  • Aurora Kinase A / genetics
  • Catalytic Domain
  • Crystallography, X-Ray
  • Humans
  • Models, Molecular
  • Mutation, Missense
  • Phosphorylation
  • Protein Processing, Post-Translational
  • Protein Structure, Secondary

Substances

  • AURKA protein, human
  • Aurora Kinase A

Associated data

  • PDB/4CEG