6g2i
From Proteopedia
(Difference between revisions)
Line 3: | Line 3: | ||
<StructureSection load='6g2i' size='340' side='right' caption='[[6g2i]], [[Resolution|resolution]] 5.90Å' scene=''> | <StructureSection load='6g2i' size='340' side='right' caption='[[6g2i]], [[Resolution|resolution]] 5.90Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
- | <table><tr><td colspan='2'>[[6g2i]] is a 18 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6G2I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6G2I FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6g2i]] is a 18 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6G2I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6G2I FirstGlance]. <br> |
</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr> | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr> | ||
+ | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ACACA, ACAC, ACC1, ACCA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), BRCA1, RNF53 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RING-type_E3_ubiquitin_transferase RING-type E3 ubiquitin transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.2.27 2.3.2.27] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RING-type_E3_ubiquitin_transferase RING-type E3 ubiquitin transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.2.27 2.3.2.27] </span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6g2i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6g2i OCA], [http://pdbe.org/6g2i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6g2i RCSB], [http://www.ebi.ac.uk/pdbsum/6g2i PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6g2i ProSAT]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6g2i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6g2i OCA], [http://pdbe.org/6g2i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6g2i RCSB], [http://www.ebi.ac.uk/pdbsum/6g2i PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6g2i ProSAT]</span></td></tr> | ||
Line 13: | Line 14: | ||
== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/ACACA_HUMAN ACACA_HUMAN]] Catalyzes the rate-limiting reaction in the biogenesis of long-chain fatty acids. Carries out three functions: biotin carboxyl carrier protein, biotin carboxylase and carboxyltransferase.<ref>PMID:20952656</ref> [[http://www.uniprot.org/uniprot/BRCA1_HUMAN BRCA1_HUMAN]] E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. It is unclear whether it also mediates the formation of other types of polyubiquitin chains. The E3 ubiquitin-protein ligase activity is required for its tumor suppressor function. The BRCA1-BARD1 heterodimer coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability. Regulates centrosomal microtubule nucleation. Required for normal cell cycle progression from G2 to mitosis. Required for appropriate cell cycle arrests after ionizing irradiation in both the S-phase and the G2 phase of the cell cycle. Involved in transcriptional regulation of P21 in response to DNA damage. Required for FANCD2 targeting to sites of DNA damage. May function as a transcriptional regulator. Inhibits lipid synthesis by binding to inactive phosphorylated ACACA and preventing its dephosphorylation. Contributes to homologous recombination repair (HRR) via its direct interaction with PALB2, fine-tunes recombinational repair partly through its modulatory role in the PALB2-dependent loading of BRCA2-RAD51 repair machinery at DNA breaks. Component of the BRCA1-RBBP8 complex which regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage via BRCA1-mediated ubiquitination of RBBP8.<ref>PMID:10500182</ref> <ref>PMID:10724175</ref> <ref>PMID:11836499</ref> <ref>PMID:12890688</ref> <ref>PMID:12887909</ref> <ref>PMID:14976165</ref> <ref>PMID:14990569</ref> <ref>PMID:16818604</ref> <ref>PMID:16326698</ref> <ref>PMID:18056443</ref> <ref>PMID:17525340</ref> <ref>PMID:19261748</ref> <ref>PMID:19369211</ref> <ref>PMID:20351172</ref> <ref>PMID:20364141</ref> | [[http://www.uniprot.org/uniprot/ACACA_HUMAN ACACA_HUMAN]] Catalyzes the rate-limiting reaction in the biogenesis of long-chain fatty acids. Carries out three functions: biotin carboxyl carrier protein, biotin carboxylase and carboxyltransferase.<ref>PMID:20952656</ref> [[http://www.uniprot.org/uniprot/BRCA1_HUMAN BRCA1_HUMAN]] E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. It is unclear whether it also mediates the formation of other types of polyubiquitin chains. The E3 ubiquitin-protein ligase activity is required for its tumor suppressor function. The BRCA1-BARD1 heterodimer coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability. Regulates centrosomal microtubule nucleation. Required for normal cell cycle progression from G2 to mitosis. Required for appropriate cell cycle arrests after ionizing irradiation in both the S-phase and the G2 phase of the cell cycle. Involved in transcriptional regulation of P21 in response to DNA damage. Required for FANCD2 targeting to sites of DNA damage. May function as a transcriptional regulator. Inhibits lipid synthesis by binding to inactive phosphorylated ACACA and preventing its dephosphorylation. Contributes to homologous recombination repair (HRR) via its direct interaction with PALB2, fine-tunes recombinational repair partly through its modulatory role in the PALB2-dependent loading of BRCA2-RAD51 repair machinery at DNA breaks. Component of the BRCA1-RBBP8 complex which regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage via BRCA1-mediated ubiquitination of RBBP8.<ref>PMID:10500182</ref> <ref>PMID:10724175</ref> <ref>PMID:11836499</ref> <ref>PMID:12890688</ref> <ref>PMID:12887909</ref> <ref>PMID:14976165</ref> <ref>PMID:14990569</ref> <ref>PMID:16818604</ref> <ref>PMID:16326698</ref> <ref>PMID:18056443</ref> <ref>PMID:17525340</ref> <ref>PMID:19261748</ref> <ref>PMID:19369211</ref> <ref>PMID:20351172</ref> <ref>PMID:20364141</ref> | ||
+ | <div style="background-color:#fffaf0;"> | ||
+ | == Publication Abstract from PubMed == | ||
+ | Acetyl-CoA carboxylase catalyses the ATP-dependent carboxylation of acetyl-CoA, a rate-limiting step in fatty acid biosynthesis(1,2). Eukaryotic acetyl-CoA carboxylases are large, homodimeric multienzymes. Human acetyl-CoA carboxylase occurs in two isoforms: the metabolic, cytosolic ACC1, and ACC2, which is anchored to the outer mitochondrial membrane and controls fatty acid beta-oxidation(1,3). ACC1 is regulated by a complex interplay of phosphorylation, binding of allosteric regulators and protein-protein interactions, which is further linked to filament formation(1,4-8). These filaments were discovered in vitro and in vivo 50 years ago(7,9,10), but the structural basis of ACC1 polymerization and regulation remains unknown. Here, we identify distinct activated and inhibited ACC1 filament forms. We obtained cryo-electron microscopy structures of an activated filament that is allosterically induced by citrate (ACC-citrate), and an inactivated filament form that results from binding of the BRCT domains of the breast cancer type 1 susceptibility protein (BRCA1). While non-polymeric ACC1 is highly dynamic, filament formation locks ACC1 into different catalytically competent or incompetent conformational states. This unique mechanism of enzyme regulation via large-scale conformational changes observed in ACC1 has potential uses in engineering of switchable biosynthetic systems. Dissecting the regulation of acetyl-CoA carboxylase opens new paths towards counteracting upregulation of fatty acid biosynthesis in disease. | ||
+ | |||
+ | Structural basis for regulation of human acetyl-CoA carboxylase.,Hunkeler M, Hagmann A, Stuttfeld E, Chami M, Guri Y, Stahlberg H, Maier T Nature. 2018 Jun 13. pii: 10.1038/s41586-018-0201-4. doi:, 10.1038/s41586-018-0201-4. PMID:29899443<ref>PMID:29899443</ref> | ||
+ | |||
+ | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
+ | </div> | ||
+ | <div class="pdbe-citations 6g2i" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
+ | [[Category: Human]] | ||
[[Category: RING-type E3 ubiquitin transferase]] | [[Category: RING-type E3 ubiquitin transferase]] | ||
[[Category: Chami, M]] | [[Category: Chami, M]] |
Revision as of 05:59, 27 June 2018
Warning: this is a large structure, and loading might take a long time or not happen at all.
Filament of acetyl-CoA carboxylase and BRCT domains of BRCA1 (ACC-BRCT) at 5.9 A resolution
|