Mutations in BRCA1/BARD1 RING-domain heterodimer: Difference between revisions

Revision as of 11:38, 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

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To begin with scenes, please click in the following order: "Mutation ...", after that on "Wild type", "Mutation" and so on.

Mutation L22S: and the . . . Putative new hydrogen bonds were added.
Mutation T37K: and the . . .
Mutation C39R: and the . . . This mutation causes missing of S-Zn bond.
. and the . . This mutation causes missing of N-Zn bond.
. and the . . This mutation causes missing of S-Zn bond.
. and the . This mutation causes missing of S-Zn bond.
. and the . This mutation causes missing of S-Zn bond.

Benign mutations

. and the . .
. and the . .

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

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Alexander Berchansky, Jaime Prilusky, Joel L. Sussman, Michal Harel

[1] 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

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 *'''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.
 *'''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>.
-*'''Mutation C39R:''' <scene name='75/751104/C39r/1'>Wild type</scene> and the <jmol><jmolButton><script>frame next</script><text>Mutation</text></jmolButton></jmol>. <scene name='75/751104/Cv/15'>Mutation C39R</scene>. <scene name='75/751104/Cv/16'>Click here to see animation of this scene</scene>. This mutation causes missing of S-Zn bond.
+*'''Mutation C39R:''' <scene name='75/751104/C39r/1'>Wild type</scene> and the <jmol><jmolButton><script>frame next</script><text>Mutation</text></jmolButton></jmol>. <scene name='75/751104/Cv/15'>Mutated and wildtype residues together</scene>. <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>. 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>. This mutation causes missing of S-Zn bond.