Crystal structure of the cell-cycle regulatory monopolar spindle one binder (LdMOB1) protein: Identification of...

Area of Science:

• Molecular Biology
• Structural Biology
• Cell Biology

Background:

• Monopolar spindle One Binder (MOB1) proteins are critical cell cycle regulators and tumor suppressors.
• MOB1 acts as an adaptor in the Hippo signaling pathway, linking MST1/2 and LATS1 kinases.
• Evolutionary conservation of MOB proteins is noted, with variations in N-terminal regions and phosphorylation sites.

Purpose of the Study:

• To determine the crystal structure of Leishmania donovani MOB1 (LdMOB1).
• To investigate the phosphorylation status and potential phosphorylation sites of LdMOB1.

Main Methods:

• X-ray crystallography was used to determine the LdMOB1 structure at 1.3 Å resolution.
• Phosphorylation assays were performed on native and T14A mutant LdMOB1.
• Computational protein-protein interaction studies were conducted.

Main Results:

• The crystal structure of LdMOB1 revealed a compact, globular conformation with conserved core architecture but variable N- and C-termini.
• Phosphorylation assays demonstrated that LdMOB1 undergoes reversible phosphorylation.
• Potential phosphorylation sites were identified at Ser 167 and Thr 170, differing from human MOB1 sites.

Conclusions:

• LdMOB1 shares structural similarities with homologs but possesses unique phosphorylation sites.
• The identified phosphorylation sites (Ser 167, Thr 170) are distinct from human MOB1 and are likely involved in LdMOB1 regulation.
• These findings contribute to understanding MOB1 protein function and regulation across species.