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Science 8 November 1996: Vol. 274. no. 5289, pp. 1001 - 1005 DOI: 10.1126/science.274.5289.1001
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Reports
Structure of the p53 Tumor Suppressor Bound to the Ankyrin and
SH3 Domains of 53BP2
Svetlana Gorina
and
Nikola P. Pavletich
Mutations in the p53 tumor suppressor are among the most
frequently observed genetic alterations in human cancer and map to the
200-amino acid core domain of the protein. The core domain contains
the sequence-specific DNA binding activity and the in vitro 53BP2
protein binding activity of p53. The crystal structure of the p53 core
domain bound to the 53BP2 protein, which contains an SH3 (Src homology
3) domain and four ankyrin repeats, revealed that (i) the SH3 domain
binds the L3 loop of p53 in a manner distinct from that of previously
characterized SH3-polyproline peptide complexes, and (ii) an ankyrin
repeat, which forms an L-shaped structure consisting of a hairpin
and two helices, binds the L2 loop of p53. The structure of the
complex shows that the 53BP2 binding site on the p53 core domain
consists of evolutionarily conserved regions that are frequently
mutated in cancer and that it overlaps the site of DNA binding. The six
most frequently observed p53 mutations disrupt 53BP2 binding in vitro.
The structure provides evidence that the 53BP2-p53 complex forms in
vivo and may have a critical role in the p53 pathway of tumor
suppression.
Cellular Biochemistry and Biophysics Program, Memorial
Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Read the Full Text
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- A Deubiquitinating Enzyme UBPY Interacts with the Src Homology 3 Domain of Hrs-binding Protein via a Novel Binding Motif PX(V/I)(D/N)RXXKP.
- M. Kato, K. Miyazawa, and N. Kitamura (2000)
J. Biol. Chem.
275, 37481-37487
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- Yes-associated Protein and p53-binding Protein-2 Interact through Their WW and SH3 Domains.
- X. Espanel and M. Sudol (2001)
J. Biol. Chem.
276, 14514-14523
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- High Thermostability and Lack of Cooperative DNA Binding Distinguish the p63 Core Domain from the Homologous Tumor Suppressor p53.
- C. Klein, G. Georges, K.-P. Kunkele, R. Huber, R. A. Engh, and S. Hansen (2001)
J. Biol. Chem.
276, 37390-37401
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- NMR Spectroscopy Reveals the Solution Dimerization Interface of p53 Core Domains Bound to Their Consensus DNA.
- C. Klein, E. Planker, T. Diercks, H. Kessler, K.-P. Kunkele, K. Lang, S. Hansen, and M. Schwaiger (2001)
J. Biol. Chem.
276, 49020-49027
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- A peptide that binds and stabilizes p53 core domain: Chaperone strategy for rescue of oncogenic mutants.
- A. Friedler, L. O. Hansson, D. B. Veprintsev, S. M. V. Freund, T. M. Rippin, P. V. Nikolova, M. R. Proctor, S. Rudiger, and A. R. Fersht (2002)
PNAS
99, 937-942
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- CLIPR-59, a new trans-Golgi/TGN cytoplasmic linker protein belonging to the CLIP-170 family.
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J. Cell Biol.
156, 631-642
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