Lefan Yu
Institut de Biologie Structurale, Institut de Recherche Interdisciplinaire de Grenoble
This thesis investigates the role of intrinsic disorder in
influenza virus replication, focusing on the intrinsically disordered region of host protein ANP32A. We report the discovery of a novel ternary complex where the viral polymerase and nucleoprotein simultaneously share a single, extended binding motif on human ANP32A. This represents a novel mode of protein interaction, driven by dynamic multivalent colocalization rather than competition. This unique mode of colocalization explains the fundamental role of ANP32A in influenza host adaptation. By analyzing binding kinetics based on NMR CPMG relaxation dispersion, we characterize the mechanism behind this novel mode of protein-protein interaction mediated by a disordered protein. In addition, these findings reveal the potential to develop inhibitors for influenza replication.