Mutations in BRCA1/BARD1 RING-domain heterodimer: Difference between revisions
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<StructureSection load='1jm7.pdb' size='450' side='right' caption='' scene='75/751104/Cv/2' pspeed='8'> | <StructureSection load='1jm7.pdb' size='450' side='right' caption='Human BRCA1 ring domain complex with BARD1 ring domain and Zn+2 ions (PDB code [[1jm7]])' scene='75/751104/Cv/2' pspeed='8'> | ||
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.<ref>PMID: 11573085</ref> | 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.<ref>PMID: 11573085</ref> | ||
<scene name='75/751104/Cv/28'>Pathogenic and benign mutations in RING domain</scene>. <font color='magenta'><b>Pathogenic mutations are shown in magenta</b></font>, <font color='lime'><b>benign mutations are shown in green</b></font>. | <scene name='75/751104/Cv/28'>Pathogenic and benign mutations in RING domain</scene>. <font color='magenta'><b>Pathogenic mutations are shown in magenta</b></font>, <font color='lime'><b>benign mutations are shown in green</b></font>. | ||