Ph.d. Defense | The Role of the FAT Domain in Controlling Localization and Activation of the Focal Adhesion Kinase (FAK)

Nov 04 2019 01:00 PM - Nov 04 2019 03:00 PM


Abstract:

Focal adhesion kinase (FAK) controls the assembly of focal adhesion sites and transduces signals from several membrane receptors. Controlled activation and localization of FAK functionally link cell adhesion, migration, and survival. FAK is overexpressed in many cancer types, promoting tumor invasiveness and metastasis. The molecular mechanisms allowing FAK to fulfill numerous different functions and act as versatile 'nanomachines' are poorly understood. We have previously revealed that ligand-induced dimerization along with intramolecular interactions control FAK activation and localization where the C-terminal focal adhesion targeting (FAT) domain is strictly involved. In this study, we combine NMR with X-ray crystallography, as well as biophysical and computational methods to understand the molecular mechanisms that link the large-scale dynamics and intramolecular and intermolecular interactions of FAT into FAK's capacity to integrate various stimuli into a site-specific function. Our results reveal FAT-mediated dynamical interplays between binding of known and newly discovered FAT ligands, and multimerization and autoactivation of FAK. Additionally, we investigate the impact of neuronal alternative splicing on FAT dynamics and interactions. Collectively, our results elucidate FAT's role in allosterically controlling various FAK functions, and might inspire allosteric protein-protein interaction inhibitors against FAK-dependent cancer cell proliferation.

Bio:

PhD candidate, studying structure and function of key complexes involved in focal adhesion assembly and control. She uses a combination of biophysical assays in addition to computational and cell biology methods. Ms Naser obtained her Master degree from the American University of Beirut (Lebanon) in the field of Neuroscience.