2B9D

Crystal Structure of HPV E7 CR3 domain

Summary for 2B9D

• Entry DOI: 10.2210/pdb2b9d/pdb
• Descriptor: E7 protein, ZINC ION (3 entities in total)
• Functional Keywords: zinc finger, homodimer, transcription, viral protein
• Biological source: Human papillomavirus type 1a
• Cellular location: Host cytoplasm : P06465
• Total number of polymer chains: 2
• Total formula weight: 11985.03

Authors

Liu, X.,Clements, A.,Zhao, K.,Marmorstein, R. (deposition date: 2005-10-11, release date: 2005-10-25, Last modification date: 2024-02-14)

Primary citation

Liu, X.,Clements, A.,Zhao, K.,Marmorstein, R.
Structure of the human Papillomavirus E7 oncoprotein and its mechanism for inactivation of the retinoblastoma tumor suppressor.
J.Biol.Chem., 281:578-586, 2006

PubMed Abstract: The E7 oncoprotein from human Papillomavirus (HPV) mediates cell transformation in part by binding to the human pRb tumor suppressor protein and E2F transcription factors, resulting in the dissociation of pRb from E2F transcription factors and the premature cell progression into the S-phase of the cell cycle. This activity is mediated by the LXCXE motif and the CR3 zinc binding domain of the E7 protein. In this study we report the x-ray crystal structure of the CR3 region of HPV E7 and a structure-based mutational analysis to investigate its mode of pRb and E2F binding and E2F displacement from pRb. The structure reveals a novel zinc-bound E7-CR3 obligate homodimer that contains two surface patches of sequence conservation. Mutation of residues within these patches reveals that one patch is required for pRb binding, whereas the other is required for E2F binding. We also show that both E7-mediated interactions are required to disrupt pRb.E2F complexes. Based on these studies we present a mechanistic model for how E7 displaces E2F from pRb. Because the CR3 region of HPV E7 has no detectable homology to other human proteins, the structure-function studies presented here provide an avenue for developing small molecule compounds that inhibit HPV-E7-mediated cell transformation.

PubMed: 16249186
DOI: 10.1074/jbc.M508455200

Experimental method

X-RAY DIFFRACTION (1.6 Å)