1t2u
From Proteopedia
(New page: 200px<br /> <applet load="1t2u" size="450" color="white" frame="true" align="right" spinBox="true" caption="1t2u, resolution 2.80Å" /> '''Structural basis of...) |
|||
Line 1: | Line 1: | ||
- | [[Image:1t2u.gif|left|200px]]<br /> | + | [[Image:1t2u.gif|left|200px]]<br /><applet load="1t2u" size="350" color="white" frame="true" align="right" spinBox="true" |
- | <applet load="1t2u" size=" | + | |
caption="1t2u, resolution 2.80Å" /> | caption="1t2u, resolution 2.80Å" /> | ||
'''Structural basis of phosphopeptide recognition by the BRCT domain of BRCA1: structure of BRCA1 missense variant V1809F'''<br /> | '''Structural basis of phosphopeptide recognition by the BRCT domain of BRCA1: structure of BRCA1 missense variant V1809F'''<br /> | ||
==Overview== | ==Overview== | ||
- | The BRCT repeats in BRCA1 are essential for its tumor suppressor activity | + | The BRCT repeats in BRCA1 are essential for its tumor suppressor activity and interact with phosphorylated protein targets containing the sequence pSer-X-X-Phe, where X indicates any residue. The structure of the tandem BRCA1 BRCT repeats bound to an optimized phosphopeptide reveals that the N-terminal repeat harbors a conserved BRCT phosphoserine-binding pocket, while the interface between the repeats forms a hydrophobic groove that recognizes the phenylalanine. Crystallographic and biochemical data suggest that the structural integrity of both binding sites is essential for peptide recognition. The diminished peptide-binding capacity observed for cancer-associated BRCA1-BRCT variants may explain the enhanced cancer risks associated with these mutations. |
==Disease== | ==Disease== | ||
Line 11: | Line 10: | ||
==About this Structure== | ==About this Structure== | ||
- | 1T2U is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with CO and SO4 as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1T2U is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CO:'>CO</scene> and <scene name='pdbligand=SO4:'>SO4</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T2U OCA]. |
==Reference== | ==Reference== | ||
Line 17: | Line 16: | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
- | [[Category: Duong, D | + | [[Category: Duong, D D.]] |
- | [[Category: Glover, J | + | [[Category: Glover, J N.M.]] |
- | [[Category: Lee, M | + | [[Category: Lee, M S.]] |
- | [[Category: Williams, R | + | [[Category: Williams, R S.]] |
[[Category: CO]] | [[Category: CO]] | ||
[[Category: SO4]] | [[Category: SO4]] | ||
Line 28: | Line 27: | ||
[[Category: phospho-peptide]] | [[Category: phospho-peptide]] | ||
- | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:09:19 2008'' |
Revision as of 13:09, 21 February 2008
|
Structural basis of phosphopeptide recognition by the BRCT domain of BRCA1: structure of BRCA1 missense variant V1809F
Contents |
Overview
The BRCT repeats in BRCA1 are essential for its tumor suppressor activity and interact with phosphorylated protein targets containing the sequence pSer-X-X-Phe, where X indicates any residue. The structure of the tandem BRCA1 BRCT repeats bound to an optimized phosphopeptide reveals that the N-terminal repeat harbors a conserved BRCT phosphoserine-binding pocket, while the interface between the repeats forms a hydrophobic groove that recognizes the phenylalanine. Crystallographic and biochemical data suggest that the structural integrity of both binding sites is essential for peptide recognition. The diminished peptide-binding capacity observed for cancer-associated BRCA1-BRCT variants may explain the enhanced cancer risks associated with these mutations.
Disease
Known diseases associated with this structure: Breast cancer-1 OMIM:[113705], Breast-ovarian cancer OMIM:[113705], Ovarian cancer OMIM:[113705], Papillary serous carcinoma of the peritoneum OMIM:[113705]
About this Structure
1T2U is a Single protein structure of sequence from Homo sapiens with and as ligands. Full crystallographic information is available from OCA.
Reference
Structural basis of phosphopeptide recognition by the BRCT domain of BRCA1., Williams RS, Lee MS, Hau DD, Glover JN, Nat Struct Mol Biol. 2004 Jun;11(6):519-25. Epub 2004 May 9. PMID:15133503
Page seeded by OCA on Thu Feb 21 15:09:19 2008
Categories: Homo sapiens | Single protein | Duong, D D. | Glover, J N.M. | Lee, M S. | Williams, R S. | CO | SO4 | Brca1 | Brct | Missense mutation | Phospho-peptide