1oqa: Difference between revisions

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[[Image:1oqa.gif|left|200px]]
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[[Image:1oqa.png|left|200px]]


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{{STRUCTURE_1oqa|  PDB=1oqa  |  SCENE=  }}  
{{STRUCTURE_1oqa|  PDB=1oqa  |  SCENE=  }}  


'''Solution structure of the BRCT-c domain from human BRCA1'''
===Solution structure of the BRCT-c domain from human BRCA1===




==Overview==
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BRCA1 is a tumor suppressor protein associated with breast and ovarian cancer. The C-terminal region of BRCA1 consists of two closely spaced BRCT domains which mediate essential biological functions, including regulation of transcription and control of cell-cycle progression by their interaction with phosphorylated effector proteins. Here we report the NMR structure of the isolated C-terminal BRCT domain (BRCT-c) from human BRCA1. BRCT-c is well-structured in solution, folding independently in the absence of its BRCT-n counterpart. Ultracentrifugation experiments and size exclusion chromatography reveal that BRCT-c exists as a monomer under near-physiological conditions. Dynamics measurements from NMR data show three loops which coincide with the most variable sequence regions in BRCT domains, to be genuinely flexible in solution. The solution structure of BRCT-c shows subtle conformational changes when compared to the crystal structure of BRCT-c in the tandem repeat of BRCA1. These affect sites involved in formation of the BRCT-n-BRCT-c interface and the binding to phosphoserine-containing peptides. The results suggest that the presence of native BRCT-n and a properly aligned BRCT-n-BRCT-c interface are essential if BRCT-c is to adopt a biologically active conformation. Structural consequences of cancer-associated mutations and biological implications of the dynamic behavior are discussed.
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==Disease==
==Disease==
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==About this Structure==
==About this Structure==
1OQA is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OQA OCA].  
1OQA is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OQA OCA].  


==Reference==
==Reference==
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[[Category: Brct]]
[[Category: Brct]]
[[Category: Breast cancer]]
[[Category: Breast cancer]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 04:09:19 2008''
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 6 00:55:58 2008''

Revision as of 00:55, 6 July 2008

File:1oqa.png

Template:STRUCTURE 1oqa

Solution structure of the BRCT-c domain from human BRCA1Solution structure of the BRCT-c domain from human BRCA1

Template:ABSTRACT PUBMED 15609993

DiseaseDisease

Known disease 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 StructureAbout this Structure

1OQA is a Single protein structure of sequence from Homo sapiens. Full experimental information is available from OCA.

ReferenceReference

Solution structure, backbone dynamics, and association behavior of the C-terminal BRCT domain from the breast cancer-associated protein BRCA1., Gaiser OJ, Ball LJ, Schmieder P, Leitner D, Strauss H, Wahl M, Kuhne R, Oschkinat H, Heinemann U, Biochemistry. 2004 Dec 28;43(51):15983-95. PMID:15609993

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