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

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  </jmolLink>
  </jmolLink>
</jmol> between the two states. Putative new hydrogen bonds were added.
</jmol> between the two states. Putative new hydrogen bonds were added.
 
*<scene name='75/751104/T37k/3'>Mutation T37K:</scene>
 
<jmol>
 
<jmolLink>
*'''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>.   
  <script>
    animation on; animation mode loop; frame 1 1 play; animation off; frame 1; select [THR]37;color selectionHalos green;selectionHalos on;
  </script>
<text>Wild type </text> 
</jmolLink>
</jmol>
conformation and
<jmol>
<jmolLink>
  <script>
    animation on; animation mode loop; frame 2 2 play; animation off; frame 2; select [LYS]37;color selectionHalos red;selectionHalos on;
  </script>
  <text>mutation.
  </text>
</jmolLink>
</jmol>
Click here to see the
<jmol>
<jmolLink>
  <script>
    animation off; frame all; select [LYS]37;color selectionHalos red;selectionHalos on;
  </script>
  <text>mutated and wild type
  </text>
</jmolLink>
</jmol> residues together, and an
<jmol>
<jmolLink>
  <script>
  animation on; animation mode loop; frame play; select [LYS]37;color selectionHalos red;selectionHalos on;
  </script>
  <text>animation
  </text>
</jmolLink>
</jmol> between the two states.   
*'''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.
*'''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.
*'''Mutation H41R:''' <scene name='75/751104/H41r/5'>Wild type</scene> and the <jmol><jmolButton><script>frame next</script><text>Mutation</text></jmolButton></jmol>. <scene name='75/751104/H41r/3'>Mutated and wildtype residues together</scene>. <scene name='75/751104/H41r/4'>Click here to see animation of this scene</scene>. This mutation causes missing of N-Zn bond.
*'''Mutation H41R:''' <scene name='75/751104/H41r/5'>Wild type</scene> and the <jmol><jmolButton><script>frame next</script><text>Mutation</text></jmolButton></jmol>. <scene name='75/751104/H41r/3'>Mutated and wildtype residues together</scene>. <scene name='75/751104/H41r/4'>Click here to see animation of this scene</scene>. This mutation causes missing of N-Zn bond.

Revision as of 12:00, 16 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

  • .

conformation and Click here to see the residues together, and an between the two states. Putative new hydrogen bonds were added.

conformation and Click here to see the residues together, and an between the two states.

  • 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 . . .

PDB ID 1jm71.pdb

Drag the structure with the mouse to rotate

References

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