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1n5o
From Proteopedia
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[[Image:1n5o.gif|left|200px]] | [[Image:1n5o.gif|left|200px]] | ||
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'''Structural consequences of a cancer-causing BRCA1-BRCT missense mutation''' | '''Structural consequences of a cancer-causing BRCA1-BRCT missense mutation''' | ||
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[[Category: Glover, J N.M.]] | [[Category: Glover, J N.M.]] | ||
[[Category: Williams, R S.]] | [[Category: Williams, R S.]] | ||
| - | [[Category: | + | [[Category: Brca1]] |
| - | [[Category: | + | [[Category: Brct]] |
| - | [[Category: | + | [[Category: Breast cancer]] |
| - | [[Category: | + | [[Category: Missense mutation]] |
| - | [[Category: | + | [[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 | + | |
Revision as of 23:07, 2 May 2008
Structural consequences of a cancer-causing BRCA1-BRCT missense mutation
Contents |
Overview
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 --> 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.
Disease
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 Structure
1N5O is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
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 Page seeded by OCA on Sat May 3 02:07:29 2008
