STRUCTURAL DETERMINANTS DRIVING THE BINDING BETWEEN PDZ2 DOMAIN OF ZO1 PROTEIN AND VIRAL SLIM SEQUENCES

The Envelope (E) protein is one of the main structural proteins that participates in many aspects of the viral life cycle such as virus maturation, assembly, and virulence mechanisms. [1] The E protein possesses a PDZ-binding motif (PBM) at its C-terminus that allows it to interact with the host PDZ domain containing proteins. One of the main binding partners of the E protein is ZO1, a protein with a crucial role in the formation of epithelial and endothelial tight junctions (TJs). [2,3] Particularly, E protein is directly involved in the mechanism of virus infection due to the presence in its primary sequence of Short Linear Motif (also known SLIM) that are responsible of protein-protein interaction with the PDZ2 domain of ZO1. Since the molecular details of such interaction have not been established, we performed a multidisciplinary study made up of experimental NMR techniques and computational docking to provide the structural determinants that drive the binding process between E-SLIM peptides and PDZ2-ZO1. This work could provide novel insights for the elucidation of the molecular mechanisms involved in the insurgence of the viral infections.