Figure 7: Schematic model of Nek7 activation by Nek9 binding and induced dimerization.

The autoinhibited state of Nek7 (grey) is characterized by the Tyr-down conformation, in which the active site is blocked by a collapsed set of four R-spine residues (green). Autophosphorylation of Nek7 is slow and can be accelerated by mutation (Tyr97 and Lys96) or Nek9. Binding of self-associated Nek9 induces back-to-back dimerization of Nek7, which releases autoinhibition by promoting a Tyr-up conformation. Nek7 autophosphorylation results in an active kinase conformation. Once phosphorylated, Nek7 can remain bound to Nek9, but Nek9 is no longer required for Nek7 activity. Phosphorylation of Nek7 by Nek9 kinase activity is an alternative mechanism in vivo.