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Yorodumi- EMDB-4344: Filament of acetyl-CoA carboxylase and BRCT domains of BRCA1 (ACC... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-4344 | ||||||||||||
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Title | Filament of acetyl-CoA carboxylase and BRCT domains of BRCA1 (ACC-BRCT) at 5.9 A resolution | ||||||||||||
Map data | |||||||||||||
Sample |
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Function / homology | Function and homology information fatty-acyl-CoA biosynthetic process / Defective HLCS causes multiple carboxylase deficiency / Biotin transport and metabolism / Defective DNA double strand break response due to BRCA1 loss of function / Defective DNA double strand break response due to BARD1 loss of function / : / BRCA1-BARD1 complex / acetyl-CoA carboxylase / : / BRCA1-C complex ...fatty-acyl-CoA biosynthetic process / Defective HLCS causes multiple carboxylase deficiency / Biotin transport and metabolism / Defective DNA double strand break response due to BRCA1 loss of function / Defective DNA double strand break response due to BARD1 loss of function / : / BRCA1-BARD1 complex / acetyl-CoA carboxylase / : / BRCA1-C complex / BRCA1-B complex / BRCA1-A complex / random inactivation of X chromosome / negative regulation of centriole replication / gamma-tubulin ring complex / Fatty acyl-CoA biosynthesis / acetyl-CoA metabolic process / negative regulation of intracellular estrogen receptor signaling pathway / malonyl-CoA biosynthetic process / nuclear ubiquitin ligase complex / acetyl-CoA carboxylase activity / ChREBP activates metabolic gene expression / DNA strand resection involved in replication fork processing / chordate embryonic development / negative regulation of fatty acid biosynthetic process / cellular response to indole-3-methanol / homologous recombination / lateral element / tissue homeostasis / XY body / protein K6-linked ubiquitination / regulation of DNA damage checkpoint / dosage compensation by inactivation of X chromosome / negative regulation of gene expression via chromosomal CpG island methylation / Carnitine metabolism / Impaired BRCA2 binding to PALB2 / protein metabolic process / : / mitotic G2/M transition checkpoint / postreplication repair / DNA repair complex / RNA polymerase binding / centrosome cycle / Defective homologous recombination repair (HRR) due to BRCA1 loss of function / Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function / Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function / Homologous DNA Pairing and Strand Exchange / Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA) / Resolution of D-loop Structures through Holliday Junction Intermediates / HDR through Single Strand Annealing (SSA) / Impaired BRCA2 binding to RAD51 / intracellular non-membrane-bounded organelle / response to ionizing radiation / DNA-binding transcription activator activity / Transcriptional Regulation by E2F6 / lipid homeostasis / mitotic G2 DNA damage checkpoint signaling / Presynaptic phase of homologous DNA pairing and strand exchange / negative regulation of cell cycle / positive regulation of vascular endothelial growth factor production / negative regulation of reactive oxygen species metabolic process / localization / regulation of DNA repair / protein autoubiquitination / SUMOylation of DNA damage response and repair proteins / ubiquitin ligase complex / negative regulation of extrinsic apoptotic signaling pathway via death domain receptors / positive regulation of DNA repair / Meiotic synapsis / tubulin binding / Activation of gene expression by SREBF (SREBP) / male germ cell nucleus / chromosome segregation / cellular response to ionizing radiation / TP53 Regulates Transcription of DNA Repair Genes / Nonhomologous End-Joining (NHEJ) / double-strand break repair via homologous recombination / RING-type E3 ubiquitin transferase / HDR through Homologous Recombination (HRR) / G2/M DNA damage checkpoint / Metalloprotease DUBs / fibrillar center / Meiotic recombination / negative regulation of cell growth / protein polyubiquitination / cellular response to prostaglandin E stimulus / ubiquitin-protein transferase activity / fatty acid biosynthetic process / positive regulation of angiogenesis / KEAP1-NFE2L2 pathway / intrinsic apoptotic signaling pathway in response to DNA damage / double-strand break repair / actin cytoskeleton / p53 binding / Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks / Neddylation / chromosome / Processing of DNA double-strand break ends / cellular response to tumor necrosis factor / protein homotetramerization Similarity search - Function | ||||||||||||
Biological species | Homo sapiens (human) | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 5.9 Å | ||||||||||||
Authors | Hunkeler M / Hagmann A / Stuttfeld E / Chami M / Stahlberg H / Maier T | ||||||||||||
Funding support | Switzerland, 3 items
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Citation | Journal: Nature / Year: 2018 Title: Structural basis for regulation of human acetyl-CoA carboxylase. Authors: Moritz Hunkeler / Anna Hagmann / Edward Stuttfeld / Mohamed Chami / Yakir Guri / Henning Stahlberg / Timm Maier / Abstract: Acetyl-CoA carboxylase catalyses the ATP-dependent carboxylation of acetyl-CoA, a rate-limiting step in fatty acid biosynthesis. Eukaryotic acetyl-CoA carboxylases are large, homodimeric multienzymes. ...Acetyl-CoA carboxylase catalyses the ATP-dependent carboxylation of acetyl-CoA, a rate-limiting step in fatty acid biosynthesis. 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 β-oxidation. ACC1 is regulated by a complex interplay of phosphorylation, binding of allosteric regulators and protein-protein interactions, which is further linked to filament formation. These filaments were discovered in vitro and in vivo 50 years ago, 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. | ||||||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_4344.map.gz | 31.6 MB | EMDB map data format | |
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Header (meta data) | emd-4344-v30.xml emd-4344.xml | 15.3 KB 15.3 KB | Display Display | EMDB header |
Images | emd_4344.png | 48.4 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-4344 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-4344 | HTTPS FTP |
-Related structure data
Related structure data | 6g2iMC 4342C 4343C 6g2dC 6g2hC C: citing same article (ref.) M: atomic model generated by this map |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_4344.map.gz / Format: CCP4 / Size: 202.8 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Voxel size | X=Y=Z: 1.058 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
-Entire : acetyl-CoA carboxylase and BRCT
Entire | Name: acetyl-CoA carboxylase and BRCT |
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Components |
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-Supramolecule #1: acetyl-CoA carboxylase and BRCT
Supramolecule | Name: acetyl-CoA carboxylase and BRCT / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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-Supramolecule #2: Acetyl-CoA carboxylase 1
Supramolecule | Name: Acetyl-CoA carboxylase 1 / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1 |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
-Supramolecule #3: Breast cancer type 1 susceptibility protein
Supramolecule | Name: Breast cancer type 1 susceptibility protein / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2 |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Escherichia coli (E. coli) |
-Macromolecule #1: Acetyl-CoA carboxylase 1
Macromolecule | Name: Acetyl-CoA carboxylase 1 / type: protein_or_peptide / ID: 1 / Number of copies: 10 / Enantiomer: LEVO / EC number: acetyl-CoA carboxylase |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 265.949344 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MDEPSPLAQP LELNQHSRFI IGSVSEDNSE DEISNLVKLD LLEEKEGSLS PASVGSDTLS DLGISSLQDG LALHIRSSMS GLHLVKQGR DRKKIDSQRD FTVASPAEFV TRFGGNKVIE KVLIANNGIA AVKCMRSIRR WSYEMFRNER AIRFVVMVTP E DLKANAEY ...String: MDEPSPLAQP LELNQHSRFI IGSVSEDNSE DEISNLVKLD LLEEKEGSLS PASVGSDTLS DLGISSLQDG LALHIRSSMS GLHLVKQGR DRKKIDSQRD FTVASPAEFV TRFGGNKVIE KVLIANNGIA AVKCMRSIRR WSYEMFRNER AIRFVVMVTP E DLKANAEY IKMADHYVPV PGGPNNNNYA NVELILDIAK RIPVQAVWAG WGHASENPKL PELLLKNGIA FMGPPSQAMW AL GDKIASS IVAQTAGIPT LPWSGSGLRV DWQENDFSKR ILNVPQELYE KGYVKDVDDG LQAAEEVGYP VMIKASEGGG GKG IRKVNN ADDFPNLFRQ VQAEVPGSPI FVMRLAKQSR HLEVQILADQ YGNAISLFGR DCSVQRRHQK IIEEAPATIA TPAV FEHME QCAVKLAKMV GYVSAGTVEY LYSQDGSFYF LELNPRLQVE HPCTEMVADV NLPAAQLQIA MGIPLYRIKD IRMMY GVSP WGDSPIDFED SAHVPCPRGH VIAARITSEN PDEGFKPSSG TVQELNFRSN KNVWGYFSVA AAGGLHEFAD SQFGHC FSW GENREEAISN MVVALKELSI RGDFRTTVEY LIKLLETESF QMNRIDTGWL DRLIAEKVQA ERPDTMLGVV CGALHVA DV SLRNSVSNFL HSLERGQVLP AHTLLNTVDV ELIYEGVKYV LKVTRQSPNS YVVIMNGSCV EVDVHRLSDG GLLLSYDG S SYTTYMKEEV DRYRITIGNK TCVFEKENDP SVMRSPSAGK LIQYIVEDGG HVFAGQCYAE IEVMKMVMTL TAVESGCIH YVKRPGAALD PGCVLAKMQL DNPSKVQQAE LHTGSLPRIQ STALRGEKLH RVFHYVLDNL VNVMNGYCLP DPFFSSKVKD WVERLMKTL RDPSLPLLEL QDIMTSVSGR IPPNVEKSIK KEMAQYASNI TSVLCQFPSQ QIANILDSHA ATLNRKSERE V FFMNTQSI VQLVQRYRSG IRGHMKAVVM DLLRQYLRVE TQFQNGHYDK CVFALREENK SDMNTVLNYI FSHAQVTKKN LL VTMLIDQ LCGRDPTLTD ELLNILTELT QLSKTTNAKV ALRARQVLIA SHLPSYELRH NQVESIFLSA IDMYGHQFCI ENL QKLILS ETSIFDVLPN FFYHSNQVVR MAALEVYVRR AYIAYELNSV QHRQLKDNTC VVEFQFMLPT SHPNRGNIPT LNRM SFSSN LNHYGMTHVA SVSDVLLDNS FTPPCQRMGG MVSFRTFEDF VRIFDEVMGC FSDSPPQ(SEP)PT FPEAGHTSLY D EDKVPRDE PIHILNVAIK TDCDIEDDRL AAMFREFTQQ NKATLVDHGI RRLTFLVAQK DFRKQVNYEV DRRFHREFPK FF TFRARDK FEEDRIYRHL EPALAFQLEL NRMRNFDLTA IPCANHKMHL YLGAAKVEVG TEVTDYRFFV RAIIRHSDLV TKE ASFEYL QNEGERLLLE AMDELEVAFN NTNVRTDCNH IFLNFVPTVI MDPSKIEESV RSMVMRYGSR LWKLRVLQAE LKIN IRLTP TGKAIPIRLF LTNESGYYLD ISLYKEVTDS RTAQIMFQAY GDKQGPLHGM LINTPYVTKD LLQSKRFQAQ SLGTT YIYD IPEMFRQSLI KLWESMSTQA FLPSPPLPSD MLTYTELVLD DQGQLVHMNR LPGGNEIGMV AWKMTFKSPE YPEGRD IIV IGNDITYRIG SFGPQEDLLF LRASELARAE GIPRIYVSAN SGARIGLAEE IRHMFHVAWV DPEDPYKGYR YLYLTPQ DY KRVSALNSVH CEHVEDEGES RYKITDIIGK EEGIGPENLR GSGMIAGESS LAYNEIITIS LVTCRAIGIG AYLVRLGQ R TIQVENSHLI LTGAGALNKV LGREVYTSNN QLGGIQIMHN NGVTHCTVCD DFEGVFTVLH WLSYMPKSVH SSVPLLNSK DPIDRIIEFV PTKTPYDPRW MLAGRPHPTQ KGQWLSGFFD YGSFSEIMQP WAQTVVVGRA RLGGIPVGVV AVETRTVELS IPADPANLD SEAKIIQQAG QVWFPDSAFK TYQAIKDFNR EGLPLMVFAN WRGFSGGMKD MYDQVLKFGA YIVDGLRECC Q PVLVYIPP QAELRGGSWV VIDSSINPRH MEMYADRESR GSVLEPEGTV EIKFRRKDLV KTMRRVDPVY IHLAERLGTP EL STAERKE LENKLKEREE FLIPIYHQVA VQFADLHDTP GRMQEKGVIS DILDWKTSRT FFYWRLRRLL LEDLVKKKIH NAN PELTDG QIQAMLRRWF VEVEGTVKAY VWDNNKDLAE WLEKQLTEED GVHSVIEENI KCISRDYVLK QIRSLVQANP EVAM DSIIH MTQHISPTQR AEVIRILSTM DSPST |
-Macromolecule #2: Breast cancer type 1 susceptibility protein
Macromolecule | Name: Breast cancer type 1 susceptibility protein / type: protein_or_peptide / ID: 2 / Number of copies: 8 / Enantiomer: LEVO / EC number: RING-type E3 ubiquitin transferase |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 27.664869 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: MKHHHHHHPM TSLYKKAGLE NLYFQGVNKR MSMVVSGLTP EEFMLVYKFA RKHHITLTNL ITEETTHVVM KTDAEFVCER TLKYFLGIA GGKWVVSYFW VTQSIKERKM LNEHDFEVRG DVVNGRNHQG PKRARESQDR KIFRGLEICC YGPFTNMPTD Q LEWMVQLC ...String: MKHHHHHHPM TSLYKKAGLE NLYFQGVNKR MSMVVSGLTP EEFMLVYKFA RKHHITLTNL ITEETTHVVM KTDAEFVCER TLKYFLGIA GGKWVVSYFW VTQSIKERKM LNEHDFEVRG DVVNGRNHQG PKRARESQDR KIFRGLEICC YGPFTNMPTD Q LEWMVQLC GASVVKELSS FTLGTGVHPI VVVQPDAWTE DNGFHAIGQM CEAPVVTREW VLDSVALYQC QELDTYLIPQ IP |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | filament |
-Sample preparation
Buffer | pH: 8 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 1.0 e/Å2 Details: Collected in movie-mode with total dose of 80 e-/A2 for a total of 80 frames. Frames 3-22 were used for final reconstruction |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: OTHER Details: Initial model was generated form 2D class averages using e2initialmodel.py in EMAN2. PDB IDs: 2yl2; 5i87; 4asi; 4y18 |
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Initial angle assignment | Type: OTHER |
Final angle assignment | Type: OTHER |
Final reconstruction | Applied symmetry - Point group: C2 (2 fold cyclic) / Resolution.type: BY AUTHOR / Resolution: 5.9 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION (ver. 2.01) / Number images used: 48483 |