2H1L

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

Crystal structure of SV40 large T-antigen bound to p53: interplay between a viral oncoprotein and a cellular tumor suppressor.

The transformation potential of SV40 depends on the activities of (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.

The structure reveals an unexpected hexameric complex of LTag binding six p53 monomers.

it 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.

summary: 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.

chains A,B and C show SV40

chains M,N and C show Cellular tumor antigen p53

PDB ID (PDB)