Mutations in BRCA1/BARD1 RING-domain heterodimer: Difference between revisions
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*<scene name='75/751104/Cv/21'>Pathogenic mutations in RING domain</scene>. | *<scene name='75/751104/Cv/21'>Pathogenic mutations in RING domain</scene>. | ||
To begin with scenes, please click in the following order: "Mutation ...", after that on "Wild type", "Mutation" and so on. | To begin with scenes, please click in the following order: "Mutation ...", after that on "Wild type", "Mutation" and so on. | ||
*'''Mutation L22S''' | *'''Mutation L22S:''' <scene name='75/751104/L22s/3'>Wild type</scene> and the <jmol><jmolButton><script>frame next</script><text>Mutation</text></jmolButton></jmol>. <scene name='75/751104/L22s/1'>Mutated and wildtype residues together</scene>. <scene name='75/751104/L22s/2'>Click here to see animation of this scene</scene>. Putative new hydrogen bonds were added. | ||
*<scene name='75/751104/T37k/ | *'''Mutation T37K:''' <scene name='75/751104/T37k/3'>Wild type</scene> and the <jmol><jmolButton><script>frame next</script><text>Mutation</text></jmolButton></jmol>. <scene name='75/751104/T37k/1'>Mutated and wildtype residues together</scene>. <scene name='75/751104/T37k/2'>Click here to see animation of this scene</scene>. | ||
*<scene name='75/751104/Cv/15'>Mutation C39R</scene>. <jmol><jmolButton><script>frame 1</script><text>Wild type</text></jmolButton></jmol> and the <jmol><jmolButton><script>frame next</script><text>Mutation</text></jmolButton></jmol>. <scene name='75/751104/Cv/16'>Click here to see animation of this scene</scene> | *<scene name='75/751104/Cv/15'>Mutation C39R</scene>. <jmol><jmolButton><script>frame 1</script><text>Wild type</text></jmolButton></jmol> and the <jmol><jmolButton><script>frame next</script><text>Mutation</text></jmolButton></jmol>. <scene name='75/751104/Cv/16'>Click here to see animation of this scene</scene>. This mutation causes missing of S-Zn bond. | ||
*<scene name='75/751104/H41r/3'>Mutation H41R</scene>. <jmol><jmolButton><script>frame 1</script><text>Wild type</text></jmolButton></jmol> and the <jmol><jmolButton><script>frame next</script><text>Mutation</text></jmolButton></jmol>. <scene name='75/751104/H41r/4'>Click here to see animation of this scene</scene> | *<scene name='75/751104/H41r/3'>Mutation H41R</scene>. <jmol><jmolButton><script>frame 1</script><text>Wild type</text></jmolButton></jmol> and the <jmol><jmolButton><script>frame next</script><text>Mutation</text></jmolButton></jmol>. <scene name='75/751104/H41r/4'>Click here to see animation of this scene</scene>. This mutation causes missing of N-Zn bond. | ||
*<scene name='75/751104/C44s/1'>Mutation C44S</scene>. <jmol><jmolButton><script>frame 1</script><text>Wild type</text></jmolButton></jmol> and the <jmol><jmolButton><script>frame next</script><text>Mutation</text></jmolButton></jmol>. <scene name='75/751104/C44s/2'>Click here to see animation of this scene</scene> | *<scene name='75/751104/C44s/1'>Mutation C44S</scene>. <jmol><jmolButton><script>frame 1</script><text>Wild type</text></jmolButton></jmol> and the <jmol><jmolButton><script>frame next</script><text>Mutation</text></jmolButton></jmol>. <scene name='75/751104/C44s/2'>Click here to see animation of this scene</scene>. This mutation causes missing of S-Zn bond. | ||
*<scene name='75/751104/C44y/1'>Mutation C44Y</scene>. <jmol><jmolButton><script>frame 1</script><text>Wild type</text></jmolButton></jmol> and the <jmol><jmolButton><script>frame next</script><text>Mutation</text></jmolButton></jmol>. <scene name='75/751104/C44y/2'>Click here to see animation of this scene</scene> | *<scene name='75/751104/C44y/1'>Mutation C44Y</scene>. <jmol><jmolButton><script>frame 1</script><text>Wild type</text></jmolButton></jmol> and the <jmol><jmolButton><script>frame next</script><text>Mutation</text></jmolButton></jmol>. <scene name='75/751104/C44y/2'>Click here to see animation of this scene</scene> This mutation causes missing of S-Zn bond. | ||
*<scene name='75/751104/C61g/1'>Mutation C61G</scene>. <jmol><jmolButton><script>frame 1</script><text>Wild type</text></jmolButton></jmol> and the <jmol><jmolButton><script>frame next</script><text>Mutation</text></jmolButton></jmol>. <scene name='75/751104/C61g/2'>Click here to see animation of this scene</scene> | *<scene name='75/751104/C61g/1'>Mutation C61G</scene>. <jmol><jmolButton><script>frame 1</script><text>Wild type</text></jmolButton></jmol> and the <jmol><jmolButton><script>frame next</script><text>Mutation</text></jmolButton></jmol>. <scene name='75/751104/C61g/2'>Click here to see animation of this scene</scene> This mutation causes missing of S-Zn bond. | ||
==Benign mutations== | ==Benign mutations== | ||
*<scene name='75/751104/Cv/24'>Mutation K45Q</scene>. <jmol><jmolButton><script>frame 1</script><text>Wild type</text></jmolButton></jmol> and the <jmol><jmolButton><script>frame next</script><text>Mutation</text></jmolButton></jmol>. <scene name='75/751104/Cv/25'>Click here to see animation of this scene</scene> | *<scene name='75/751104/Cv/24'>Mutation K45Q</scene>. <jmol><jmolButton><script>frame 1</script><text>Wild type</text></jmolButton></jmol> and the <jmol><jmolButton><script>frame next</script><text>Mutation</text></jmolButton></jmol>. <scene name='75/751104/Cv/25'>Click here to see animation of this scene</scene>. | ||
*<scene name='75/751104/Cv/11'>Mutation D67Y</scene>. <jmol><jmolButton><script>frame 1</script><text>Wild type</text></jmolButton></jmol> and the <jmol><jmolButton><script>frame next</script><text>Mutation</text></jmolButton></jmol>. <scene name='75/751104/Cv/10'>Click here to see animation of this scene</scene> | *<scene name='75/751104/Cv/11'>Mutation D67Y</scene>. <jmol><jmolButton><script>frame 1</script><text>Wild type</text></jmolButton></jmol> and the <jmol><jmolButton><script>frame next</script><text>Mutation</text></jmolButton></jmol>. <scene name='75/751104/Cv/10'>Click here to see animation of this scene</scene>. | ||
</StructureSection> | </StructureSection> | ||
== References == | == References == | ||
Revision as of 11:32, 5 February 2017
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.[1] . Pathogenic mutations are shown in magenta, benign mutations are shown in green. Pathogenic mutations
To begin with scenes, please click in the following order: "Mutation ...", after that on "Wild type", "Mutation" and so on.
Benign mutations
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References
- ↑ Brzovic PS, Rajagopal P, Hoyt DW, King MC, Klevit RE. Structure of a BRCA1-BARD1 heterodimeric RING-RING complex. Nat Struct Biol. 2001 Oct;8(10):833-7. PMID:11573085 doi:10.1038/nsb1001-833