1n5o: Difference between revisions

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[[Image:1n5o.gif|left|200px]]
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{{STRUCTURE_1n5o|  PDB=1n5o  |  SCENE=  }}  
{{STRUCTURE_1n5o|  PDB=1n5o  |  SCENE=  }}  


'''Structural consequences of a cancer-causing BRCA1-BRCT missense mutation'''
===Structural consequences of a cancer-causing BRCA1-BRCT missense mutation===




==Overview==
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The integrity of the carboxyl-terminal BRCT repeat region is critical for BRCA1 tumor suppressor function; however, the molecular details of how a number of clinically derived BRCT missense mutations affect BRCA1 function remain largely unknown. Here we assess the structural response of the BRCT tandem repeat domain to a well characterized, cancer-associated single amino acid substitution, Met-1775 --&gt; Arg-1775. The structure of BRCT-M1775R reveals that the mutated side chain is extruded from the protein hydrophobic core, thereby altering the protein surface. Charge-charge repulsion, rearrangement of the hydrophobic core, and disruption of the native hydrogen bonding network at the interface between the two BRCT repeats contribute to the conformational instability of BRCT-M1775R. Destabilization and global unfolding of the mutated BRCT domain at physiological temperatures explain the pleiotropic molecular and genetic defects associated with the BRCA1-M1775R protein.
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{{ABSTRACT_PUBMED_12427738}}


==Disease==
==Disease==
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[[Category: Missense mutation]]
[[Category: Missense mutation]]
[[Category: Protein folding]]
[[Category: Protein folding]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 02:07:29 2008''
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 07:25:49 2008''

Revision as of 07:25, 29 July 2008

File:1n5o.png

Template:STRUCTURE 1n5o

Structural consequences of a cancer-causing BRCA1-BRCT missense mutationStructural consequences of a cancer-causing BRCA1-BRCT missense mutation

Template:ABSTRACT PUBMED 12427738

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

1N5O is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

Structural consequences of a cancer-causing BRCA1-BRCT missense mutation., Williams RS, Glover JN, J Biol Chem. 2003 Jan 24;278(4):2630-5. Epub 2002 Nov 8. PMID:12427738

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