Molecular dynamic simulations suggest the existence of two TPX2-dependent switches for Aurora A activation. 1) TPX2 binding to Aurora A forces lysine residue K143 of AURKA into an “open” state, which pulls ADP out of the ATP binding site in AURKA to promote kinase activation. 2) Arginine residue R180 of AURKA undergoes a “closed” movement upon TPX2 binding, thus capturing phosphorylated threonine T288 of AURKA into a buried position and locking AURKA in its active conformation. The existence of two TPX2-dependent switches in AURKA activation was further verified by the analysis of two AURKA mutants (K143A and R180A) (Xu et al. 2011).AURKA activation is enabled through phosphorylation and TPX2 binding; these two activating switches act synergistically and withough a predefined order (Dodson and Bayliss 2012).
Dodson, CA, Bayliss, R
Sardon, T, Bayliss, R, Conti, E, Vernos, I
Li, Y, Wang, X, Wang, Y, Xiao, Z, Xu, X
protein serine/threonine kinase activity of Centrosome:AURKA:TPX2:HMMR [cytosol]
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