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1miu
From Proteopedia
(New page: 200px<br /> <applet load="1miu" size="450" color="white" frame="true" align="right" spinBox="true" caption="1miu, resolution 3.1Å" /> '''Structure of a BRCA2...) |
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| - | [[Image:1miu.gif|left|200px]]<br /> | + | [[Image:1miu.gif|left|200px]]<br /><applet load="1miu" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1miu" size=" | + | |
caption="1miu, resolution 3.1Å" /> | caption="1miu, resolution 3.1Å" /> | ||
'''Structure of a BRCA2-DSS1 complex'''<br /> | '''Structure of a BRCA2-DSS1 complex'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Mutations in the BRCA2 (breast cancer susceptibility gene 2) tumor | + | Mutations in the BRCA2 (breast cancer susceptibility gene 2) tumor suppressor lead to chromosomal instability due to defects in the repair of double-strand DNA breaks (DSBs) by homologous recombination, but BRCA2's role in this process has been unclear. Here, we present the 3.1 angstrom crystal structure of a approximately 90-kilodalton BRCA2 domain bound to DSS1, which reveals three oligonucleotide-binding (OB) folds and a helix-turn-helix (HTH) motif. We also (i) demonstrate that this BRCA2 domain binds single-stranded DNA, (ii) present its 3.5 angstrom structure bound to oligo(dT)9, (iii) provide data that implicate the HTH motif in dsDNA binding, and (iv) show that BRCA2 stimulates RAD51-mediated recombination in vitro. These findings establish that BRCA2 functions directly in homologous recombination and provide a structural and biochemical basis for understanding the loss of recombination-mediated DSB repair in BRCA2-associated cancers. |
==Disease== | ==Disease== | ||
| Line 11: | Line 10: | ||
==About this Structure== | ==About this Structure== | ||
| - | 1MIU is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with HG as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1MIU is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with <scene name='pdbligand=HG:'>HG</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MIU OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Chen, P | + | [[Category: Chen, P L.]] |
| - | [[Category: Jeffrey, P | + | [[Category: Jeffrey, P D.]] |
[[Category: Kinnucan, E.]] | [[Category: Kinnucan, E.]] | ||
| - | [[Category: Lee, W | + | [[Category: Lee, W H.]] |
[[Category: Miller, J.]] | [[Category: Miller, J.]] | ||
| - | [[Category: Pavletich, N | + | [[Category: Pavletich, N P.]] |
[[Category: Sun, Y.]] | [[Category: Sun, Y.]] | ||
| - | [[Category: Thoma, N | + | [[Category: Thoma, N H.]] |
[[Category: Yang, H.]] | [[Category: Yang, H.]] | ||
[[Category: Zheng, N.]] | [[Category: Zheng, N.]] | ||
| Line 33: | Line 32: | ||
[[Category: tumor suppressor]] | [[Category: tumor suppressor]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:55:36 2008'' |
Revision as of 11:55, 21 February 2008
|
Structure of a BRCA2-DSS1 complex
Contents |
Overview
Mutations in the BRCA2 (breast cancer susceptibility gene 2) tumor suppressor lead to chromosomal instability due to defects in the repair of double-strand DNA breaks (DSBs) by homologous recombination, but BRCA2's role in this process has been unclear. Here, we present the 3.1 angstrom crystal structure of a approximately 90-kilodalton BRCA2 domain bound to DSS1, which reveals three oligonucleotide-binding (OB) folds and a helix-turn-helix (HTH) motif. We also (i) demonstrate that this BRCA2 domain binds single-stranded DNA, (ii) present its 3.5 angstrom structure bound to oligo(dT)9, (iii) provide data that implicate the HTH motif in dsDNA binding, and (iv) show that BRCA2 stimulates RAD51-mediated recombination in vitro. These findings establish that BRCA2 functions directly in homologous recombination and provide a structural and biochemical basis for understanding the loss of recombination-mediated DSB repair in BRCA2-associated cancers.
Disease
Known disease associated with this structure: Split hand/foot malformation, type 1 OMIM:[183600]
About this Structure
1MIU is a Protein complex structure of sequences from Homo sapiens and Mus musculus with as ligand. Full crystallographic information is available from OCA.
Reference
BRCA2 function in DNA binding and recombination from a BRCA2-DSS1-ssDNA structure., Yang H, Jeffrey PD, Miller J, Kinnucan E, Sun Y, Thoma NH, Zheng N, Chen PL, Lee WH, Pavletich NP, Science. 2002 Sep 13;297(5588):1837-48. PMID:12228710
Page seeded by OCA on Thu Feb 21 13:55:36 2008
