Viral oncoprotein inactivation of p53

Their crystal structure of the large T antigen/p53 complex interaction will be featured on the September 1st cover of G&D (see accompanying image).

The Simian Virus 40 (SV40) genome encodes a large tumor antigen (LTag) protein, which is synthesized early on and is necessary for productive viral infection. Once inside a host cell, LTag interacts with the p53 and Rb tumor suppressor proteins and renders them inactive. p53 and Rb inhibition drives cells into S phase, promoting both host and viral genome replication. Owing to LTag's ability to overtake cellular growth control, and thereby induce tumors in animals, LTag is classified as a viral oncoprotein.

Dr. Chen and colleagues reveal that the LTag-p53 complex is comprised of a hexameric LTag protein bound to six p53 molecules. Their structure illustrates how p53 protein conformation changes upon LTag binding, and thereby prevents p53 binding to DNA.

Dr. Chen explains that “The X-ray structure provides a molecular explanation for the oncogenesis potential of the virus oncoprotein LTag. LTag induces the conformational change of p53 protein through physical interactions. By doing so, LTag abolishes the tumor suppressor function of p53, which can lead to genomic instability and tumor formation”.