1ycs
From Proteopedia
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| , resolution 2.2Å | |||||||
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| Ligands: | |||||||
| Gene: | RESIDUES 291-529 (Homo sapiens) | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
P53-53BP2 COMPLEX
Contents |
Overview
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 beta hairpin and two alpha 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.
Disease
Known diseases associated with this structure: Adrenal cortical carcinoma OMIM:[191170], Breast cancer OMIM:[191170], Colorectal cancer OMIM:[191170], Hepatocellular carcinoma OMIM:[191170], Histiocytoma OMIM:[191170], Li-Fraumeni syndrome OMIM:[191170], Multiple malignancy syndrome OMIM:[191170], Nasopharyngeal carcinoma OMIM:[191170], Osteosarcoma OMIM:[191170], Pancreatic cancer OMIM:[191170], Thyroid carcinoma OMIM:[191170]
About this Structure
1YCS is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structure of the p53 tumor suppressor bound to the ankyrin and SH3 domains of 53BP2., Gorina S, Pavletich NP, Science. 1996 Nov 8;274(5289):1001-5. PMID:8875926
Page seeded by OCA on Thu Mar 20 15:21:13 2008
