Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comment
. 1996 Nov 8;274(5289):948-53.
doi: 10.1126/science.274.5289.948.

Structure of the MDM2 oncoprotein bound to the p53 tumor suppressor transactivation domain

P H Kussie  1 , S Gorina, V Marechal, B Elenbaas, J Moreau, A J Levine, N P Pavletich
Affiliations
Comment

Structure of the MDM2 oncoprotein bound to the p53 tumor suppressor transactivation domain

P H Kussie et al. Science. .

Abstract

The MDM2 oncoprotein is a cellular inhibitor of the p53 tumor suppressor in that it can bind the transactivation domain of p53 and downregulate its ability to activate transcription. In certain cancers, MDM2 amplification is a common event and contributes to the inactivation of p53. The crystal structure of the 109-residue amino-terminal domain of MDM2 bound to a 15-residue transactivation domain peptide of p53 revealed that MDM2 has a deep hydrophobic cleft on which the p53 peptide binds as an amphipathic alpha helix. The interface relies on the steric complementarity between the MDM2 cleft and the hydrophobic face of the p53 alpha helix and, in particular, on a triad of p53 amino acids-Phe19, Trp23, and Leu26-which insert deep into the MDM2 cleft. These same p53 residues are also involved in transactivation, supporting the hypothesis that MDM2 inactivates p53 by concealing its transactivation domain. The structure also suggests that the amphipathic alpha helix may be a common structural motif in the binding of a diverse family of transactivation factors to the TATA-binding protein-associated factors.

PubMed Disclaimer

Comment on

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

Publication types

MeSH terms