SUMOylation of LKB1: Computational Insights towards Cell Growth Regulation

Author : Bita Amiri hazaveh, Maryam Azimzadeh Irani, Mahdieh Alamdari

Abstract :SUMOylation, a reversible post-translational modification in which SUMO (Small Ubiquitin-Like Modifier) covalently attaches to substrate proteins, modulates diverse cellular functions. LKB1 (also known as STK11), a tumor suppressor kinase, plays a critical role in cell polarity, energy metabolism, and growth regulation. In this study, we performed a computational analysis to investigate the structural and functional impact of SUMOylation of LKB1 on its interaction with key partners MO25 and STRADα. Structural models of LKB1, SUMO1, MO25, and STRADα were obtained from the PDB, and SUMOylation was modeled by linking SUMO1 to lysine 178 of LKB1. Molecular docking revealed that SUMOylation significantly reduced the binding affinity and stability of the LKB1-MO25 and LKB1 STRADα complexes, as indicated by increased RMSD and decreased buried surface area. Residue-level interaction analysis further confirmed altered binding interfaces upon SUMOylation. These findings suggest that SUMOylation of LKB1 may regulate its activity by modulating complex stability and partner interactions

Keywords :LKB1, molecular modeling, post-translational modification, SUMOylation.

Conference Name :International Conference on Bioinformatics and Molecular Biology (ICBMB-25)

Conference Place Shanghai, China

Conference Date 21st Aug 2025