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BP: Fachverband Biologische Physik

BP 3: Computational Biophysics I

BP 3.1: Talk

Monday, March 27, 2023, 09:30–09:45, BAR 0106

Elucidating the Binding Process of a Disordered Protein to a Membrane Containing Ionic Lipids via Atomistic Simulations: a Case Study of LKB1 — •Azadeh Alavizargar and Andreas Heuer — Institute of Physical Chemistry, University of Muenster, Corrensstr. 28/30, 48149 Muenster, Germany

Liver kinase LKB1 is a serine/threonine kinase, which apart from from playing a significant role in many biological processes such as cell proliferation and polarity, it functions also as a downregulator in tumors. In this work, we probe the significance of phosphatidic acid (PA) lipids as well as the poly-basic region for the binding of the C-terminus of the protein to the membrane, using molecular dynamics simulations. It was revealed that PA lipids are essential for the protein-membrane binding and that the mutation of the first three lysine residues does not abolish the binding. We specifically show the details of the protein-membrane binding at the atomic resolution using various amount of PA lipids in the membrane. Importantly, it was also found that the protein-membrane binding is dynamic and gives rise to structural changes of the protein as a result of the interaction and the accumulation of PA lipids in the membrane, which is beyond the accessible resolution in the corresponding experiments. Furthermore, we quantified the significance of each polar amino acid in the poly-basic region of the protein. These results provide important insights into the understanding and mechanism of the interaction of disordered proteins with membranes including ionic lipids.