Crystal Structure of the BRCA1 Associated Ring Domain (BARD1) Tandem BRCT DomainsCrystal Structure of the BRCA1 Associated Ring Domain (BARD1) Tandem BRCT Domains
Structural highlights
3fa2 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
BARD1_HUMAN Probable E3 ubiquitin-protein ligase. The BRCA1-BARD1 heterodimer specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability. Plays a central role in the control of the cell cycle in response to DNA damage. Acts by mediating ubiquitin E3 ligase activity that is required for its tumor suppressor function. Also forms a heterodimer with CSTF1/CSTF-50 to modulate mRNA processing and RNAP II stability by inhibiting pre-mRNA 3' cleavage.[1][2][3][4]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
References
↑Kleiman FE, Manley JL. Functional interaction of BRCA1-associated BARD1 with polyadenylation factor CstF-50. Science. 1999 Sep 3;285(5433):1576-9. PMID:10477523
↑Wu-Baer F, Lagrazon K, Yuan W, Baer R. The BRCA1/BARD1 heterodimer assembles polyubiquitin chains through an unconventional linkage involving lysine residue K6 of ubiquitin. J Biol Chem. 2003 Sep 12;278(37):34743-6. Epub 2003 Jul 30. PMID:12890688 doi:10.1074/jbc.C300249200
↑Morris JR, Solomon E. BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair. Hum Mol Genet. 2004 Apr 15;13(8):807-17. Epub 2004 Feb 19. PMID:14976165 doi:10.1093/hmg/ddh095
↑Wu-Baer F, Ludwig T, Baer R. The UBXN1 protein associates with autoubiquitinated forms of the BRCA1 tumor suppressor and inhibits its enzymatic function. Mol Cell Biol. 2010 Jun;30(11):2787-98. doi: 10.1128/MCB.01056-09. Epub 2010 Mar , 29. PMID:20351172 doi:10.1128/MCB.01056-09
