Mutations in BRCA1/BARD1 RING-domain heterodimer

The RING domain of the breast and ovarian cancer tumor suppressor BRCA1 interacts with multiple cognate proteins, including the RING protein BARD1. Proper function of the BRCA1 RING domain is critical, as evidenced by the many cancer-predisposing mutations found within this domain. We present the solution structure of the heterodimer formed between the RING domains of BRCA1 and BARD1. Comparison with the RING homodimer of the V(D)J recombination-activating protein RAG1 reveals the structural diversity of complexes formed by interactions between different RING domains. The BRCA1–BARD1 structure provides a model for its ubiquitin ligase activity, illustrates how the BRCA1 RING domain can be involved in associations with multiple protein partners and provides a framework for understanding cancer-causing mutations at the molecular level. . Pathogenic mutations are shown in magenta, benign mutations are shown in green. Pathogenic mutations . and this renders the Click here to see the together. Click here to of both states. Putative new hydrogen bonds were added. Mutation T37K: and the . . . Mutation C39R: and the . . . This mutation causes missing of S-Zn bond. Mutation H41R: and the . . . This mutation causes missing of N-Zn bond. Mutation C44S: and the . . . This mutation causes missing of S-Zn bond. Mutation C44Y: and the . . This mutation causes missing of S-Zn bond. Mutation C61G: and the . . This mutation causes missing of S-Zn bond. Benign mutations Mutation K45Q: and the . . . Mutation D67Y: and the . . .

spinqualitylabelsall models PDB ID 1jm71.pdb Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image