Molecular interactions important for Axl activation

AXL is a receptor tyrosine kinase that is highly expressed in several cancers, and activation of AXL is associated with cell survival, proliferation, migration and immunological response. Because AXL is involved in many cellular processes across different malignant tissue types, there is a critical need to understand and modulate Axl signaling in the tumor microenvironment. The aim of this project is to improve the understanding of the molecular mechanism of the interaction between AXL and GAS6, PtdSer, and the therapeutic antibody tilvestamab by using structural biology as a research method. The methods used are cryo-electron microscopy and X-ray crystallography. After the global Covid pandemic had started, AXL was identified as a possible binding partner of the spike protein of COVID-19. A collaboration with Professor Wendy Maury at the Universitiy of Iowa confirmed that AXL mediates an increase in COVID-19 infection. This project also showed that the mechanism is not through a direct interaction with the spike protein, but rather an interaction with a lipid in the viral membrane. These results are now part of a publication in the journal PLoS Pathogens.