User:Brian Ochoa/Sandbox 1

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== Function ==
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== Structural Highlights ==
BRCA1 is an 1,863 amino acid long protein that contains a ring finger motif from position 24 to 64. The ring motif is part of a larger domain spanning the first one hundred amino acid residues, which is required for the formation of its stable structure. This N-terminus domain is of the most highly conserved region of the BRCA1 gene and several cancer-predisposition mutations have been identified in this region.<ref>Meza, J. E., Brzovic, P. S., King, M., & Kelvin, R. E. (n.d.). Mapping the Functional Domains of BRCA1. Retrieved April 12, 2016, from http://www.jbc.org/content/274/9/5659.full#fn-5
BRCA1 is an 1,863 amino acid long protein that contains a ring finger motif from position 24 to 64. The ring motif is part of a larger domain spanning the first one hundred amino acid residues, which is required for the formation of its stable structure. This N-terminus domain is of the most highly conserved region of the BRCA1 gene and several cancer-predisposition mutations have been identified in this region.<ref>Meza, J. E., Brzovic, P. S., King, M., & Kelvin, R. E. (n.d.). Mapping the Functional Domains of BRCA1. Retrieved April 12, 2016, from http://www.jbc.org/content/274/9/5659.full#fn-5
doi: 10.1074/jbc.274.9.5659</ref> The ring motif is also a C3HC4 zinc-binding motif, named so for the conserved pattern of cysteine and histidines residues that bind the zinc ions.<ref>Borden, K. L., & Freemont, P. S. (n.d.). The RING finger domain: A recent example of a sequence—structure family. Retrieved April 12, 2016, from http://www.sciencedirect.com/science/article/pii/S0959440X96800601
doi: 10.1074/jbc.274.9.5659</ref> The ring motif is also a C3HC4 zinc-binding motif, named so for the conserved pattern of cysteine and histidines residues that bind the zinc ions.<ref>Borden, K. L., & Freemont, P. S. (n.d.). The RING finger domain: A recent example of a sequence—structure family. Retrieved April 12, 2016, from http://www.sciencedirect.com/science/article/pii/S0959440X96800601
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doi:10.1016/S0959-440X(96)80060-1</ref> Ultimately, the ring motif of BRCA1 forms a heterodimer with the ring motif of BARD1 to assemble the functional protein complex. The solution structure of this complex shows that long alpha helices border the zinc binding residues in the ring motif. These alpha helices from the ring motif’s of BRCA1 and BARD1 combine to form a four-helix bundle that stabilizes the heterodimer and positions the zinc binding regions next to one another (http://www.jbc.org/content/274/9/5659.full).
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doi:10.1016/S0959-440X(96)80060-1</ref> Ultimately, the ring motif of BRCA1 forms a heterodimer with the ring motif of BARD1 to assemble the functional protein complex. The solution structure of this complex shows that long alpha helices border the zinc binding residues in the ring motif. These alpha helices from the ring motif’s of BRCA1 and BARD1 combine to form a four-helix bundle that stabilizes the heterodimer and positions the zinc binding regions next to one another. <ref>Meza, J. E., Brzovic, P. S., King, M., & Kelvin, R. E. (n.d.). Mapping the Functional Domains of BRCA1. Retrieved April 12, 2016, from http://www.jbc.org/content/274/9/5659.full#fn-5
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== Disease ==
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doi: 10.1074/jbc.274.9.5659</ref>
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== Functional Highlights ==
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One main function of the ring finger domain of BRCA1 is to mediate heterodimer formation with BARD1. BARD1 and BRCA1 are able to form a heterodimer because they both contain ring finger domains that interact with each other. Another main function is to catalyze ubiquination of lysine residue using ubiquitin from E2 enzymes. Ubiquination of lysine-48 is a means of marking a protein for degradation by the proteasome.<ref> Morris, J. R. (2004). BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair. Human Molecular Genetics, 13(8), 807-817. doi:10.1093/hmg/ddh095
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</ref> BRCA1 also moves to areas within the cell containing damaged DNA and acts as scaffolding for repair complexes to sit.<ref>Clapperton, J. A., Manke, I. A., Lowery, D. M., Ho, T., Haire, L. F., Yaffe, M. B., & Smerdon, S. J. (2004). Structure and mechanism of BRCA1 BRCT domain recognition of phosphorylated BACH1 with implications for cancer. Nat Struct Mol Biol Nature Structural & Molecular Biology, 11(6), 512-518. doi:10.1038/nsmb775</ref> Ubiquination of lysine-63 controls DNA repair pathways as well as activate protein kinases by sending out non-proteolytic signals.<ref> Morris, J. R. (2004). BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair. Human Molecular Genetics, 13(8), 807-817. doi:10.1093/hmg/ddh095
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</ref>
== Relevance ==
== Relevance ==

Revision as of 22:26, 12 April 2016

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References

  1. ↑ Hanson, R. M., Prilusky, J., Renjian, Z., Nakane, T. and Sussman, J. L. (2013), JSmol and the Next-Generation Web-Based Representation of 3D Molecular Structure as Applied to Proteopedia. Isr. J. Chem., 53:207-216. doi:http://dx.doi.org/10.1002/ijch.201300024
  2. ↑ Herraez A. Biomolecules in the computer: Jmol to the rescue. Biochem Mol Biol Educ. 2006 Jul;34(4):255-61. doi: 10.1002/bmb.2006.494034042644. PMID:21638687 doi:10.1002/bmb.2006.494034042644
  3. ↑ Meza, J. E., Brzovic, P. S., King, M., & Kelvin, R. E. (n.d.). Mapping the Functional Domains of BRCA1. Retrieved April 12, 2016, from http://www.jbc.org/content/274/9/5659.full#fn-5 doi: 10.1074/jbc.274.9.5659
  4. ↑ Borden, K. L., & Freemont, P. S. (n.d.). The RING finger domain: A recent example of a sequence—structure family. Retrieved April 12, 2016, from http://www.sciencedirect.com/science/article/pii/S0959440X96800601 doi:10.1016/S0959-440X(96)80060-1
  5. ↑ Meza, J. E., Brzovic, P. S., King, M., & Kelvin, R. E. (n.d.). Mapping the Functional Domains of BRCA1. Retrieved April 12, 2016, from http://www.jbc.org/content/274/9/5659.full#fn-5 doi: 10.1074/jbc.274.9.5659
  6. ↑ Morris, J. R. (2004). BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair. Human Molecular Genetics, 13(8), 807-817. doi:10.1093/hmg/ddh095
  7. ↑ Clapperton, J. A., Manke, I. A., Lowery, D. M., Ho, T., Haire, L. F., Yaffe, M. B., & Smerdon, S. J. (2004). Structure and mechanism of BRCA1 BRCT domain recognition of phosphorylated BACH1 with implications for cancer. Nat Struct Mol Biol Nature Structural & Molecular Biology, 11(6), 512-518. doi:10.1038/nsmb775
  8. ↑ Morris, J. R. (2004). BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair. Human Molecular Genetics, 13(8), 807-817. doi:10.1093/hmg/ddh095

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