8GCR
HPV16 E6-E6AP-p53 complex
Summary for 8GCR
| Entry DOI | 10.2210/pdb8gcr/pdb |
| EMDB information | 29941 |
| Descriptor | Maltose/maltodextrin-binding periplasmic protein,Protein E6, Cellular tumor antigen p53, Ubiquitin-protein ligase E3A, ... (4 entities in total) |
| Functional Keywords | complex, hpv, ubiquitin ligase, tumor suppressor, viral protein |
| Biological source | Escherichia coli O157:H7 More |
| Total number of polymer chains | 3 |
| Total formula weight | 190336.02 |
| Authors | Bratkowski, M.A.,Wang, J.C.K.,Hao, Q.,Nile, A.H. (deposition date: 2023-03-02, release date: 2024-03-06) |
| Primary citation | Wang, J.C.K.,Baddock, H.T.,Mafi, A.,Foe, I.T.,Bratkowski, M.,Lin, T.Y.,Jensvold, Z.D.,Preciado Lopez, M.,Stokoe, D.,Eaton, D.,Hao, Q.,Nile, A.H. Structure of the p53 degradation complex from HPV16. Nat Commun, 15:1842-1842, 2024 Cited by PubMed Abstract: 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. These findings shed light on the molecular basis of the ternary complex, which has been pursued as a potential therapeutic target for HPV-driven cervical, anal, and oropharyngeal cancers over the last two decades. Understanding the structural and mechanistic underpinnings of this complex is crucial for developing effective therapies to combat HPV-induced cancers. Our findings may help to explain why previous attempts to disrupt this complex have failed to generate therapeutic modalities and suggest that current strategies should be reevaluated. PubMed: 38418456DOI: 10.1038/s41467-024-45920-w PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.38 Å) |
Structure validation
Download full validation report
