1kzy
From Proteopedia
(New page: 200px<br /> <applet load="1kzy" size="450" color="white" frame="true" align="right" spinBox="true" caption="1kzy, resolution 2.5Å" /> '''Crystal Structure of...) |
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| - | [[Image:1kzy.gif|left|200px]]<br /> | + | [[Image:1kzy.gif|left|200px]]<br /><applet load="1kzy" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1kzy" size=" | + | |
caption="1kzy, resolution 2.5Å" /> | caption="1kzy, resolution 2.5Å" /> | ||
'''Crystal Structure of the 53bp1 BRCT Region Complexed to Tumor Suppressor P53'''<br /> | '''Crystal Structure of the 53bp1 BRCT Region Complexed to Tumor Suppressor P53'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Brca1 C-terminal (BRCT) domains are a common protein-protein interaction | + | Brca1 C-terminal (BRCT) domains are a common protein-protein interaction motif in proteins involved in the DNA damage response and DNA repair. The DNA-damage response protein 53BP1 has two BRCT domains that bind to the DNA-binding domain of p53. The 53BP1 tandem-BRCT region is homologous to the tandem-BRCT region of Brca1, which is involved in double-strand break repair and homologous recombination and which binds BACH1, a member of the DEAH helicase family. Here we report the structures of a human 53BP1-p53 complex and of the rat Brca1 BRCT repeats. The 53BP1-p53 structure shows that the two BRCT repeats are arranged tandemly and pack extensively through an interface that also involves the inter-repeat linker. The first BRCT repeat and the linker together bind p53 on a region that overlaps with the DNA-binding surface of p53 and involves p53 residues that are mutated in cancer and are important for DNA binding. Comparison with the structure of the tandem-BRCT region of Brca1 shows a remarkable conservation of the repeat arrangement and of the inter-BRCT repeat interface. Analysis of human BRCA1 tumor-derived mutations and conservation identifies a potential protein-binding site that we show through mutagenesis is involved in BACH1 binding. The BACH1-binding region of Brca1 consists of a unique insertion in the first BRCT repeat and the inter-repeat linker and is analogous to the region of 53BP1 that binds p53. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1KZY is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with ZN as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1KZY is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=ZN:'>ZN</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KZY OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Cantor, S | + | [[Category: Cantor, S B.]] |
| - | [[Category: Finnin, M | + | [[Category: Finnin, M S.]] |
| - | [[Category: Jeffrey, P | + | [[Category: Jeffrey, P D.]] |
| - | [[Category: Joo, W | + | [[Category: Joo, W S.]] |
| - | [[Category: Livingston, D | + | [[Category: Livingston, D M.]] |
| - | [[Category: Pavletich, N | + | [[Category: Pavletich, N P.]] |
[[Category: ZN]] | [[Category: ZN]] | ||
[[Category: parallel beta sheet]] | [[Category: parallel beta sheet]] | ||
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[[Category: three-helix bundle]] | [[Category: three-helix bundle]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:39:44 2008'' |
Revision as of 11:39, 21 February 2008
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Crystal Structure of the 53bp1 BRCT Region Complexed to Tumor Suppressor P53
Contents |
Overview
Brca1 C-terminal (BRCT) domains are a common protein-protein interaction motif in proteins involved in the DNA damage response and DNA repair. The DNA-damage response protein 53BP1 has two BRCT domains that bind to the DNA-binding domain of p53. The 53BP1 tandem-BRCT region is homologous to the tandem-BRCT region of Brca1, which is involved in double-strand break repair and homologous recombination and which binds BACH1, a member of the DEAH helicase family. Here we report the structures of a human 53BP1-p53 complex and of the rat Brca1 BRCT repeats. The 53BP1-p53 structure shows that the two BRCT repeats are arranged tandemly and pack extensively through an interface that also involves the inter-repeat linker. The first BRCT repeat and the linker together bind p53 on a region that overlaps with the DNA-binding surface of p53 and involves p53 residues that are mutated in cancer and are important for DNA binding. Comparison with the structure of the tandem-BRCT region of Brca1 shows a remarkable conservation of the repeat arrangement and of the inter-BRCT repeat interface. Analysis of human BRCA1 tumor-derived mutations and conservation identifies a potential protein-binding site that we show through mutagenesis is involved in BACH1 binding. The BACH1-binding region of Brca1 consists of a unique insertion in the first BRCT repeat and the inter-repeat linker and is analogous to the region of 53BP1 that binds p53.
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
1KZY is a Protein complex structure of sequences from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
Reference
Structure of the 53BP1 BRCT region bound to p53 and its comparison to the Brca1 BRCT structure., Joo WS, Jeffrey PD, Cantor SB, Finnin MS, Livingston DM, Pavletich NP, Genes Dev. 2002 Mar 1;16(5):583-93. PMID:11877378
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