1t29
From Proteopedia
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|PDB= 1t29 |SIZE=350|CAPTION= <scene name='initialview01'>1t29</scene>, resolution 2.3Å | |PDB= 1t29 |SIZE=350|CAPTION= <scene name='initialview01'>1t29</scene>, resolution 2.3Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= | + | |LIGAND= <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1t29 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t29 OCA], [http://www.ebi.ac.uk/pdbsum/1t29 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1t29 RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
The recognition of the phosphorylated BACH1 helicase by the BRCA1 C-terminal (BRCT) repeats is important to the tumor suppressor function of BRCA1. Here we report the crystal structure of the BRCT repeats of human BRCA1 bound to a phosphorylated BACH1 peptide at 2.3 A resolution. The phosphorylated serine 990 and phenylalanine 993 of BACH1 anchor the binding to BRCA1 through specific interactions with a surface cleft at the junction of the two BRCT repeats. This surface cleft is highly conserved in BRCA1 across species, suggesting an evolutionarily conserved function of phosphopeptide recognition. Importantly, conserved amino acids critical for BACH1 binding are frequently targeted for missense mutations in breast cancer. These mutations greatly diminish the ability of BRCA1 to interact with the phosphorylated BACH1 peptide. Additional structural analysis revealed significant implications for understanding the function of the BRCT family of proteins in DNA damage and repair signaling. | The recognition of the phosphorylated BACH1 helicase by the BRCA1 C-terminal (BRCT) repeats is important to the tumor suppressor function of BRCA1. Here we report the crystal structure of the BRCT repeats of human BRCA1 bound to a phosphorylated BACH1 peptide at 2.3 A resolution. The phosphorylated serine 990 and phenylalanine 993 of BACH1 anchor the binding to BRCA1 through specific interactions with a surface cleft at the junction of the two BRCT repeats. This surface cleft is highly conserved in BRCA1 across species, suggesting an evolutionarily conserved function of phosphopeptide recognition. Importantly, conserved amino acids critical for BACH1 binding are frequently targeted for missense mutations in breast cancer. These mutations greatly diminish the ability of BRCA1 to interact with the phosphorylated BACH1 peptide. Additional structural analysis revealed significant implications for understanding the function of the BRCT family of proteins in DNA damage and repair signaling. | ||
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| - | ==Disease== | ||
| - | Known diseases associated with this structure: Breast cancer, early-onset OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=605882 605882]], Breast cancer-1 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=113705 113705]], Breast-ovarian cancer OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=113705 113705]], Fanconi anemia, complementation group J OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=605882 605882]], Ovarian cancer OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=113705 113705]], Papillary serous carcinoma of the peritoneum OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=113705 113705]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: phosphopeptide recognition]] | [[Category: phosphopeptide recognition]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 23:50:18 2008'' |
Revision as of 20:50, 30 March 2008
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| , resolution 2.3Å | |||||||
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of the BRCA1 BRCT repeats bound to a phosphorylated BACH1 peptide
Overview
The recognition of the phosphorylated BACH1 helicase by the BRCA1 C-terminal (BRCT) repeats is important to the tumor suppressor function of BRCA1. Here we report the crystal structure of the BRCT repeats of human BRCA1 bound to a phosphorylated BACH1 peptide at 2.3 A resolution. The phosphorylated serine 990 and phenylalanine 993 of BACH1 anchor the binding to BRCA1 through specific interactions with a surface cleft at the junction of the two BRCT repeats. This surface cleft is highly conserved in BRCA1 across species, suggesting an evolutionarily conserved function of phosphopeptide recognition. Importantly, conserved amino acids critical for BACH1 binding are frequently targeted for missense mutations in breast cancer. These mutations greatly diminish the ability of BRCA1 to interact with the phosphorylated BACH1 peptide. Additional structural analysis revealed significant implications for understanding the function of the BRCT family of proteins in DNA damage and repair signaling.
About this Structure
1T29 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structure of the BRCT repeats of BRCA1 bound to a BACH1 phosphopeptide: implications for signaling., Shiozaki EN, Gu L, Yan N, Shi Y, Mol Cell. 2004 May 7;14(3):405-12. PMID:15125843
Page seeded by OCA on Sun Mar 30 23:50:18 2008
