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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-23827 | |||||||||
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Title | Structure of C9orf72:SMCR8:WDR41 in complex with ARF1 | |||||||||
![]() | postprocess with deepemhancer "tightTarget" model | |||||||||
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Function / homology | ![]() Glycosphingolipid transport / mitotic cleavage furrow ingression / trans-Golgi Network Vesicle Budding / Atg1/ULK1 kinase complex / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | ![]() ![]() | |||||||||
![]() | Su M-Y / Hurley JH | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural basis for the ARF GAP activity and specificity of the C9orf72 complex. Authors: Ming-Yuan Su / Simon A Fromm / Jonathan Remis / Daniel B Toso / James H Hurley / ![]() ![]() ![]() Abstract: Mutation of C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontal temporal degeneration (FTD), which is attributed to both a gain and loss of function. C9orf72 ...Mutation of C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontal temporal degeneration (FTD), which is attributed to both a gain and loss of function. C9orf72 forms a complex with SMCR8 and WDR41, which was reported to have GTPase activating protein activity toward ARF proteins, RAB8A, and RAB11A. We determined the cryo-EM structure of ARF1-GDP-BeF bound to C9orf72:SMCR8:WDR41. The SMCR8 and C9orf72 domains form the binding pocket for ARF1. One face of the C9orf72 domain holds ARF1 in place, while the SMCR8 positions the catalytic finger Arg147 in the ARF1 active site. Mutations in interfacial residues of ARF1 and C9orf72 reduced or eliminated GAP activity. RAB8A GAP required ~10-fold higher concentrations of the C9orf72 complex than for ARF1. These data support a specific function for the C9orf72 complex as an ARF GAP. The structure also provides a model for the active forms of the longin domain GAPs of FLCN and NPRL2 that regulate the Rag GTPases of the mTORC1 pathway. | |||||||||
History |
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Structure visualization
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 62.8 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 15.7 KB 15.7 KB | Display Display | ![]() |
Images | ![]() | 37.9 KB | ||
Filedesc metadata | ![]() | 6.8 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7mgeMC M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | postprocess with deepemhancer "tightTarget" model | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.94 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
-Entire : Complex of C9orf72:SMCR8:WDR41 with ARF1
Entire | Name: Complex of C9orf72:SMCR8:WDR41 with ARF1 |
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Components |
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-Supramolecule #1: Complex of C9orf72:SMCR8:WDR41 with ARF1
Supramolecule | Name: Complex of C9orf72:SMCR8:WDR41 with ARF1 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#4 |
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Source (natural) | Organism: ![]() ![]() |
-Macromolecule #1: WD repeat-containing protein 41
Macromolecule | Name: WD repeat-containing protein 41 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 51.783805 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MLRWLIGGGR EPQGLAEKSP LQTIGEEQTQ NPYTELLVLK AHHDIVRFLV QLDDYRFASA GDDGIVVVWN AQTGEKLLEL NGHTQKITA IITFPSLESC EEKNQLILTA SADRTVIVWD GDTTRQVQRI SCFQSTVKCL TVLQRLDVWL SGGNDLCVWN R KLDLLCKT ...String: MLRWLIGGGR EPQGLAEKSP LQTIGEEQTQ NPYTELLVLK AHHDIVRFLV QLDDYRFASA GDDGIVVVWN AQTGEKLLEL NGHTQKITA IITFPSLESC EEKNQLILTA SADRTVIVWD GDTTRQVQRI SCFQSTVKCL TVLQRLDVWL SGGNDLCVWN R KLDLLCKT SHLSDTGISA LVEIPKNCVV AAVGKELIIF RLVAPTEGSL EWDILEVKRL LDHQDNILSL INVNDLSFVT GS HVGELII WDALDWTMQA YERNFWDPSP QLDTQQEIKL CQKSNDISIH HFTCDEENVF AAVGRGLYVY SLQMKRVIAC QKT AHDSNV LHVARLPNRQ LISCSEDGSV RIWELREKQQ LAAEPVPTGF FNMWGFGRVS KQASQPVKKQ QENATSCSLE LIGD LIGHS SSVEMFLYFE DHGLVTCSAD HLIILWKNGE RESGLRSLRL FQKLEENGDL YLAV UniProtKB: WD repeat-containing protein 41 |
-Macromolecule #2: Guanine nucleotide exchange protein SMCR8
Macromolecule | Name: Guanine nucleotide exchange protein SMCR8 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 105.149094 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MISAPDVVAF TKEEEYEEEP YNEPALPEEY SVPLFPFASQ GANPWSKLSG AKFSRDFILI SEFSEQVGPQ PLLTIPNDTK VFGTFDLNY FSLRIMSVDY QASFVGHPPG SAYPKLNFVE DSKVVLGDSK EGAFAYVHHL TLYDLEARGF VRPFCMAYIS A DQHKIMQQ ...String: MISAPDVVAF TKEEEYEEEP YNEPALPEEY SVPLFPFASQ GANPWSKLSG AKFSRDFILI SEFSEQVGPQ PLLTIPNDTK VFGTFDLNY FSLRIMSVDY QASFVGHPPG SAYPKLNFVE DSKVVLGDSK EGAFAYVHHL TLYDLEARGF VRPFCMAYIS A DQHKIMQQ FQELSAEFSR ASECLKTGNR KAFAGELEKK LKDLDYTRTV LHTETEIQKK ANDKGFYSSQ AIEKANELAS VE KSIIEHQ DLLKQIRSYP HRKLKGHDLC PGEMEHIQDQ ASQASTTSNP DESADTDLYT CRPAYTPKLI KAKSTKCFDK KLK TLEELC DTEYFTQTLA QLSHIEHMFR GDLCYLLTSQ IDRALLKQQH ITNFLFEDFV EVDDRMVEKQ ESIPSKPSQD RPPS SSLEE CPIPKVLISV GSYKSSVESV LIKMEQELGD EEYKEVEVTE LSSFDPQENL DYLDMDMKGS ISSGESIEVL GTEKS TSVL SKSDSQASLT VPLSPQVVRS KAVSHRTISE DSIEVLSTCP SEALIPDDFK ASYPSAINEE ESYPDGNEGA IRFQAS ISP PELGETEEGS IENTPSQIDS SCCIGKESDG QLVLPSTPAH THSDEDGVVS SPPQRHRQKD QGFRVDFSVE NANPSSR DN SCEGFPAYEL DPSHLLASRD ISKTSLDNYS DTTSYVSSVA STSSDRIPSA YPAGLSSDRH KKRAGQNALK FIRQYPFA H PAIYSLLSGR TLVVLGEDEA IVRKLVTALA IFVPSYGCYA KPVKHWASSP LHIMDFQKWK LIGLQRVASP AGAGTLHAL SRYSRYTSIL DLDNKTLRCP LYRGTLVPRL ADHRTQIKRG STYYLHVQSM LTQLCSKAFL YTFCHHLHLP THDKETEELV ASRQMSFLK LTLGLVNEDV RVVQYLAELL KLHYMQESPG TSHPMLRFDY VPSFLYKI UniProtKB: Guanine nucleotide exchange protein SMCR8 |
-Macromolecule #3: Guanine nucleotide exchange C9orf72
Macromolecule | Name: Guanine nucleotide exchange C9orf72 / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 54.391477 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MSTLCPPPSP AVAKTEIALS GKSPLLAATF AYWDNILGPR VRHIWAPKTE QVLLSDGEIT FLANHTLNGE ILRNAESGAI DVKFFVLSE KGVIIVSLIF DGNWNGDRST YGLSIILPQT ELSFYLPLHR VCVDRLTHII RKGRIWMHKE RQENVQKIIL E GTERMEDQ ...String: MSTLCPPPSP AVAKTEIALS GKSPLLAATF AYWDNILGPR VRHIWAPKTE QVLLSDGEIT FLANHTLNGE ILRNAESGAI DVKFFVLSE KGVIIVSLIF DGNWNGDRST YGLSIILPQT ELSFYLPLHR VCVDRLTHII RKGRIWMHKE RQENVQKIIL E GTERMEDQ GQSIIPMLTG EVIPVMELLS SMKSHSVPEE IDIADTVLND DDIGDSCHEG FLLNAISSHL QTCGCSVVVG SS AEKVNKI VRTLCLFLTP AERKCSRLCE AESSFKYESG LFVQGLLKDS TGSFVLPFRQ VMYAPYPTTH IDVDVNTVKQ MPP CHEHIY NQRRYMRSEL TAFWRATSEE DMAQDTIIYT DESFTPDLNI FQDVLHRDTL VKAFLDQVFQ LKPGLSLRST FLAQ FLLVL HRKALTLIKY IEDDTQKGKK PFKSLRNLKI DLDLTAEGDL NIIMALAEKI KPGLHSFIFG RPFYTSVQER DVLMT F UniProtKB: Guanine nucleotide exchange factor C9orf72 |
-Macromolecule #4: ADP-ribosylation factor 1
Macromolecule | Name: ADP-ribosylation factor 1 / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 18.994572 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: ATEMRILMVG LDAAGKTTIL YKLKLGEIVT TIPTIGFNVE TVEYKNISFT VWDVGGQDKI RPLWRHYFQN TQGLIFVVDS NDRERVNEA REELMRMLAE DELRDAVLLV FANKQDLPNA MNAAEITDKL GLHSLRHRNW YIQATCATSG DGLYEGLDWL S NQLRNQ UniProtKB: ![]() |
-Macromolecule #5: GUANOSINE-5'-DIPHOSPHATE
Macromolecule | Name: GUANOSINE-5'-DIPHOSPHATE / type: ligand / ID: 5 / Number of copies: 1 / Formula: GDP |
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Molecular weight | Theoretical: 443.201 Da |
Chemical component information | ![]() ChemComp-GDP: |
-Macromolecule #6: BERYLLIUM TRIFLUORIDE ION
Macromolecule | Name: BERYLLIUM TRIFLUORIDE ION / type: ligand / ID: 6 / Number of copies: 1 / Formula: BEF |
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Molecular weight | Theoretical: 66.007 Da |
Chemical component information | ![]() ChemComp-BEF: |
-Macromolecule #7: MAGNESIUM ION
Macromolecule | Name: MAGNESIUM ION / type: ligand / ID: 7 / Number of copies: 1 / Formula: MG |
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Molecular weight | Theoretical: 24.305 Da |
-Experimental details
-Structure determination
Method | ![]() |
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Aggregation state | particle |
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Sample preparation
Concentration | 0.16 mg/mL |
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Buffer | pH: 7.4 |
Grid | Model: C-flat-1.2/1.3 / Mesh: 300 / Pretreatment - Type: GLOW DISCHARGE |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV |
Details | concentration range of 0.16-0.2 mg/ml |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: OTHER / Imaging mode: BRIGHT FIELD![]() |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 50.0 e/Å2 |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Startup model | Type of model: PDB ENTRY |
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Initial angle assignment | Type: OTHER |
Final angle assignment | Type: OTHER |
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.94 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 796219 |
-Atomic model buiding 1
Refinement | Protocol: RIGID BODY FIT |
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Output model | ![]() PDB-7mge: |