2H1L

The Structure of the Oncoprotein SV40 Large T Antigen and p53 Tumor Suppressor Complex

Summary for 2H1L

• Entry DOI: 10.2210/pdb2h1l/pdb
• Descriptor: Large T antigen, Cellular tumor antigen p53, ZINC ION (3 entities in total)
• Functional Keywords: p53 loop-3 conformation change, viral protein
• Biological source: Simian virus 40; More
• Total number of polymer chains: 24
• Total formula weight: 786950.16

Authors

Lilyestrom, W.,Klein, M.G.,Chen, X.S. (deposition date: 2006-05-16, release date: 2006-09-12, Last modification date: 2024-11-06)

Primary citation

Lilyestrom, W.,Klein, M.G.,Zhang, R.,Joachimiak, A.,Chen, X.S.
Crystal structure of SV40 large T-antigen bound to p53: interplay between a viral oncoprotein and a cellular tumor suppressor.
Genes Dev., 20:2373-2382, 2006

PubMed Abstract: The transformation potential of Simian Virus 40 depends on the activities of large T-antigen (LTag), which interacts with several cellular tumor suppressors including the important "guardian" of the genome, p53. Inhibition of p53 function by LTag is necessary for both efficient viral replication and cellular transformation. We determined the crystal structure of LTag in complex with p53. The structure reveals an unexpected hexameric complex of LTag binding six p53 monomers. Structure-guided mutagenesis of LTag and p53 residues supported the p53-LTag interface defined by the complex structure. The structure also shows that LTag binding induces dramatic conformational changes at the DNA-binding area of p53, which is achieved partially through an unusual "methionine switch" within p53. In the complex structure, LTag occupies the whole p53 DNA-binding surface and likely interferes with formation of a functional p53 tetramer. In addition, we showed that p53 inhibited LTag helicase function through direct complex formation.

PubMed: 16951253
DOI: 10.1101/gad.1456306

Experimental method

X-RAY DIFFRACTION (3.16 Å)