Abstact

Monopolar spindle One Binder (MOB1) proteins, recently identified as tumor suppressors, are essential regulators of the cell cycle, ensuring proper chromosome segregation and ploidy maintenance during mitotic exit and transition to cytokinesis. MOB1 also works as an adaptor protein for upstream Mammalian sterile 20-like kinase (MST1/2) and downstream Large Tumor Suppressor (LATS1) kinases in the Hippo pathway. Evolutionarily conserved, MOB proteins show differences in their N-terminal region and phosphorylation sites. Here, we describe the crystal structure of Leishmania donovani MOB1 (LdMOB1) elucidated at 1.3 A. LdMOB1 adopts a compact, globular conformation, with its core architecture similar to its homologs with a conformational variability in its N- and C-termini. Phosphorylation assays of native and T14A mutant LdMOB1 revealed that LdMOB1 undergoes reversible phosphorylation. Our results suggest that the potential phosphorylation sites are Ser 167 and Thr 170, distinct from the Thr 12 and Thr 35 in human MOB1. Computational protein-protein interaction studies confirm the plausibility of the identified phosphorylation sites.