1n5o

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spinqualitylabelsall models 1n5o, resolution 2.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

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

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

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 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

1N5O is a Single protein structure of sequence from Homo sapiens with CO and SO4 as ligands. 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

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