Protein phosphorylation is one of the most important mechanisms involved in the regulation of protein-protein interactions and thus takes part in many cellular signaling pathways such as the formation and separation of mitotic spindles during cellular division. There is a family of protein kinases called NEKs which take part in the control of the machinery involved in the mitotic spindle microtubule formation. NEK9, along with NEK6 and NEK7, form a signaling cascade which is essential for mitotic progression, as it controls the formation of the mitotic spindle and the organization of centrosomes. These mechanisms must be perfectly regulated to avoid mistakes which might result in pathologies associated to cellular division, such as cancer. The research group on Protein Structure, at the Institut de Biotecnologia i de Biomedicina (IBB) in the Universitat Autònoma of Barcelona, lead by David Reverter,  has analyzed the regulation of the NEK9 kinase, which can be activated or deactivated depending on its interaction with LC8 – the regulator protein. Such regulation depends on the phosphorylation of a residue found at the interphase between the two proteins. Using protein crystallography, a technique used in structural biology which allows us to see protein and big molecular complexes at an atomic level, IBB researchers have shown how phosphorylation is enough to regulate the interaction between these two proteins:  kinase NEK9 and the regulator protein LC8. Their results shed a light on the complex regulation pathway for cell division, valuable information when it comes to finding new therapeutic strategies for complex diseases such as cancer. 

The work, published in JBC, is the first with a 3D structure done with data obtained in the BL13-XALOC beam line of the ALBA Synchrotron, and the result of a collaboration between the IBB group with researchers from the IRB Barcelona and the Institute for Biocomputation and Physics of Complex Systems at the Zaragoza University.

The figure shows crystal structures of the LC8 regulatory protein with two peptides from kinase NEK9: on the right, the interactions with a phosphorylated peptide and on the left, with a non-phosphorylated peptide. Taken from fig.2 at  Gallego et al., 2013. Structural analysis of the regulation of the DYNLL/LC8 binding to Nek9 by phosphorylation.

Interesting links:
Sincrotrón ALBA http://www.cells.es
IRB Barcelona http://www.irbbarcelona.org/index.php/en