John C K Wang, Hannah T Baddock, Amirhossein Mafi, Ian T Foe, Matthew Bratkowski, Ting-Yu Lin, Zena D Jensvold, Magdalena Preciado López, David Stokoe, Dan Eaton, Qi Hao, Aaron H Nile
Human papillomavirus (HPV) is a significant contributor to the global cancer burden, and its carcinogenic activity is facilitated in part by the HPV early protein 6 (E6), which interacts with the E3-ligase E6AP, also known as UBE3A, to promote degradation of the tumor suppressor, p53. In this study, we present a single-particle cryoEM structure of the full-length E6AP protein in complex with HPV16 E6 (16E6) and p53, determined at a resolution of ~3.3 Å. Our structure reveals extensive protein-protein interactions between 16E6 and E6AP, explaining their picomolar binding affinity...
February 28, 2024: Nature Communications