Centre for Molecular Medicine Norway (NCMM), Nordic EMBL Partnership, Faculty of Medicine, Oslo, Norway
Oda Hovet
Centre for Molecular Medicine Norway (NCMM), Nordic EMBL Partnership, Faculty of Medicine, Oslo, Norway; Department of Biosciences, University of Oslo, Oslo, Norway; Hylleraas Centre for Quantum Molecular Sciences, University of Oslo, Oslo, Norway
Hemanga Gogoi
Centre for Molecular Medicine Norway (NCMM), Nordic EMBL Partnership, Faculty of Medicine, Oslo, Norway
Jennine Dawicki-McKenna
Department of Biochemistry and Biophysics, Penn Center for Genome Integrity, Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States
Stine Malene Hansen Wøien
Centre for Molecular Medicine Norway (NCMM), Nordic EMBL Partnership, Faculty of Medicine, Oslo, Norway
Manuel Carrer
Hylleraas Centre for Quantum Molecular Sciences, University of Oslo, Oslo, Norway; Department of Chemistry, University of Oslo, Oslo, Norway
Ben E Black
Department of Biochemistry and Biophysics, Penn Center for Genome Integrity, Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States
Michele Cascella
Hylleraas Centre for Quantum Molecular Sciences, University of Oslo, Oslo, Norway; Department of Chemistry, University of Oslo, Oslo, Norway
Aurora B, together with IN-box, the C-terminal part of INCENP, forms an enzymatic complex that ensures faithful cell division. The [Aurora B/IN-box] complex is activated by autophosphorylation in the Aurora B activation loop and in IN-box, but it is not clear how these phosphorylations activate the enzyme. We used a combination of experimental and computational studies to investigate the effects of phosphorylation on the molecular dynamics and structure of [Aurora B/IN-box]. In addition, we generated partially phosphorylated intermediates to analyze the contribution of each phosphorylation independently. We found that the dynamics of Aurora and IN-box are interconnected, and IN-box plays both positive and negative regulatory roles depending on the phosphorylation status of the enzyme complex. Phosphorylation in the activation loop of Aurora B occurs intramolecularly and prepares the enzyme complex for activation, but two phosphorylated sites are synergistically responsible for full enzyme activity.
