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- EMDB-28825: Human CCC complex -

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Basic information

Entry
Database: EMDB / ID: EMD-28825
TitleHuman CCC complex
Map dataSharpened refined map from cryoSPARC
Sample
  • Complex: Human CCC complex
    • Protein or peptide: COMM domain-containing protein 1
    • Protein or peptide: COMM domain-containing protein 2
    • Protein or peptide: COMM domain-containing protein 3
    • Protein or peptide: COMM domain-containing protein 4
    • Protein or peptide: COMM domain-containing protein 5
    • Protein or peptide: COMM domain-containing protein 6
    • Protein or peptide: COMM domain-containing protein 7
    • Protein or peptide: COMM domain-containing protein 8
    • Protein or peptide: COMM domain-containing protein 9
    • Protein or peptide: COMM domain-containing protein 10
Keywordsendosomal sorting / commander / CCC complex / ENDOCYTOSIS
Function / homology
Function and homology information


negative regulation of sodium ion transmembrane transport / plasma membrane to endosome transport / regulation of proteasomal ubiquitin-dependent protein catabolic process / negative regulation of protein localization to cell surface / copper ion homeostasis / Golgi to plasma membrane transport / phosphatidic acid binding / phosphatidylinositol-3,4-bisphosphate binding / sodium channel inhibitor activity / phosphatidylinositol-3,5-bisphosphate binding ...negative regulation of sodium ion transmembrane transport / plasma membrane to endosome transport / regulation of proteasomal ubiquitin-dependent protein catabolic process / negative regulation of protein localization to cell surface / copper ion homeostasis / Golgi to plasma membrane transport / phosphatidic acid binding / phosphatidylinositol-3,4-bisphosphate binding / sodium channel inhibitor activity / phosphatidylinositol-3,5-bisphosphate binding / Cul2-RING ubiquitin ligase complex / sodium ion transport / negative regulation of NF-kappaB transcription factor activity / phosphatidylinositol-3,4,5-trisphosphate binding / NF-kappaB binding / tumor necrosis factor-mediated signaling pathway / phosphatidylinositol-4,5-bisphosphate binding / positive regulation of protein ubiquitination / cholesterol homeostasis / nucleotide-excision repair / recycling endosome / protein transport / Neddylation / cytoplasmic vesicle / secretory granule lumen / ficolin-1-rich granule lumen / early endosome / endosome membrane / endosome / copper ion binding / intracellular membrane-bounded organelle / negative regulation of DNA-templated transcription / Neutrophil degranulation / Golgi apparatus / protein homodimerization activity / extracellular region / nucleoplasm / identical protein binding / nucleus / plasma membrane / cytoplasm / cytosol
Similarity search - Function
COMM domain-containing protein 2 / COMM domain-containing protein 3 / COMM domain-containing protein 4 / : / COMMD1 N-terminal domain / COMM domain-containing protein 1 / COMM domain-containing protein 5 / COMM domain-containing protein 7 / COMM domain-containing protein 10 / : ...COMM domain-containing protein 2 / COMM domain-containing protein 3 / COMM domain-containing protein 4 / : / COMMD1 N-terminal domain / COMM domain-containing protein 1 / COMM domain-containing protein 5 / COMM domain-containing protein 7 / COMM domain-containing protein 10 / : / COMMD1 N-terminal domain / COMMD2-7/10, HN domain / COMM domain-containing protein 9 / : / COMMD9, helical N-terminal domain / COMM domain / COMM domain / COMM domain profile.
Similarity search - Domain/homology
COMM domain-containing protein 6 / COMM domain-containing protein 7 / COMM domain-containing protein 2 / COMM domain-containing protein 1 / COMM domain-containing protein 5 / COMM domain-containing protein 4 / COMM domain-containing protein 8 / COMM domain-containing protein 9 / COMM domain-containing protein 3 / COMM domain-containing protein 10
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.12 Å
AuthorsHealy MD / McNally KE / Butkovic R / Chilton M / Kato K / Sacharz J / McConville C / Moody ERR / Shaw S / Planelles-Herrero VJ ...Healy MD / McNally KE / Butkovic R / Chilton M / Kato K / Sacharz J / McConville C / Moody ERR / Shaw S / Planelles-Herrero VJ / Kadapalakere SY / Ross J / Borucu U / Palmer CS / Chen K / Croll TI / Hall RJ / Caruana NJ / Ghai R / Nguyen THD / Heesom KJ / Saitoh S / Berger I / Berger-Schaffitzel C / Williams TA / Stroud DA / Derivery E / Collins BM / Cullen PJ
Funding support United Kingdom, Australia, 9 items
OrganizationGrant numberCountry
Wellcome Trust104568/Z/14/Z United Kingdom
Wellcome Trust220260/Z/20/Z United Kingdom
Wellcome Trust220480/Z/20/Z United Kingdom
Medical Research Council (MRC, United Kingdom)MR/L007363/1 United Kingdom
Medical Research Council (MRC, United Kingdom)MR/P018807/1 United Kingdom
The Lister Institute of Preventive Medicine United Kingdom
Royal SocietyRSRP/R1/211004 United Kingdom
National Health and Medical Research Council (NHMRC, Australia)APP1136021 Australia
National Health and Medical Research Council (NHMRC, Australia)APP1156493 Australia
CitationJournal: Cell / Year: 2023
Title: Structure of the endosomal Commander complex linked to Ritscher-Schinzel syndrome.
Authors: Michael D Healy / Kerrie E McNally / Rebeka Butkovič / Molly Chilton / Kohji Kato / Joanna Sacharz / Calum McConville / Edmund R R Moody / Shrestha Shaw / Vicente J Planelles-Herrero / ...Authors: Michael D Healy / Kerrie E McNally / Rebeka Butkovič / Molly Chilton / Kohji Kato / Joanna Sacharz / Calum McConville / Edmund R R Moody / Shrestha Shaw / Vicente J Planelles-Herrero / Sathish K N Yadav / Jennifer Ross / Ufuk Borucu / Catherine S Palmer / Kai-En Chen / Tristan I Croll / Ryan J Hall / Nikeisha J Caruana / Rajesh Ghai / Thi H D Nguyen / Kate J Heesom / Shinji Saitoh / Imre Berger / Christiane Schaffitzel / Tom A Williams / David A Stroud / Emmanuel Derivery / Brett M Collins / Peter J Cullen /
Abstract: The Commander complex is required for endosomal recycling of diverse transmembrane cargos and is mutated in Ritscher-Schinzel syndrome. It comprises two sub-assemblies: Retriever composed of VPS35L, ...The Commander complex is required for endosomal recycling of diverse transmembrane cargos and is mutated in Ritscher-Schinzel syndrome. It comprises two sub-assemblies: Retriever composed of VPS35L, VPS26C, and VPS29; and the CCC complex which contains twelve subunits: COMMD1-COMMD10 and the coiled-coil domain-containing (CCDC) proteins CCDC22 and CCDC93. Combining X-ray crystallography, electron cryomicroscopy, and in silico predictions, we have assembled a complete structural model of Commander. Retriever is distantly related to the endosomal Retromer complex but has unique features preventing the shared VPS29 subunit from interacting with Retromer-associated factors. The COMMD proteins form a distinctive hetero-decameric ring stabilized by extensive interactions with CCDC22 and CCDC93. These adopt a coiled-coil structure that connects the CCC and Retriever assemblies and recruits a 16th subunit, DENND10, to form the complete Commander complex. The structure allows mapping of disease-causing mutations and reveals the molecular features required for the function of this evolutionarily conserved trafficking machinery.
History
DepositionNov 8, 2022-
Header (metadata) releaseMay 24, 2023-
Map releaseMay 24, 2023-
UpdateJun 19, 2024-
Current statusJun 19, 2024Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

Downloads & links

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Map

FileDownload / File: emd_28825.map.gz / Format: CCP4 / Size: 178 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationSharpened refined map from cryoSPARC
Voxel sizeX=Y=Z: 1.084 Å
Density
Contour LevelBy AUTHOR: 0.2
Minimum - Maximum-1.1997054 - 2.1816554
Average (Standard dev.)-0.0003661294 (±0.02851102)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions360360360
Spacing360360360
CellA=B=C: 390.24 Å
α=β=γ: 90.0 °

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Supplemental data

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Additional map: Unsharpened refined map

Fileemd_28825_additional_1.map
AnnotationUnsharpened refined map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Half map: Half map

Fileemd_28825_half_map_1.map
AnnotationHalf map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Half map: Half map

Fileemd_28825_half_map_2.map
AnnotationHalf map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Sample components

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Entire : Human CCC complex

EntireName: Human CCC complex
Components
  • Complex: Human CCC complex
    • Protein or peptide: COMM domain-containing protein 1
    • Protein or peptide: COMM domain-containing protein 2
    • Protein or peptide: COMM domain-containing protein 3
    • Protein or peptide: COMM domain-containing protein 4
    • Protein or peptide: COMM domain-containing protein 5
    • Protein or peptide: COMM domain-containing protein 6
    • Protein or peptide: COMM domain-containing protein 7
    • Protein or peptide: COMM domain-containing protein 8
    • Protein or peptide: COMM domain-containing protein 9
    • Protein or peptide: COMM domain-containing protein 10

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Supramolecule #1: Human CCC complex

SupramoleculeName: Human CCC complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: COMM domain-containing protein 1

MacromoleculeName: COMM domain-containing protein 1 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 20.863715 KDa
Recombinant expressionOrganism: Spodoptera (butterflies/moths)
SequenceString:
MAAGELEGGK PLSGLLNALA QDTFHGYPGI TEELLRSQLY PEVPPEEFRP FLAKMRGILK SIASADMDFN QLEAFLTAQT KKQGGITSD QAAVISKFWK SHKTKIRESL MNQSRWNSGL RGLSWRVDGK SQSRHSAQIH TPVAIIELEL GKYGQESEFL C LEFDEVKV NQILKTLSEV EESISTLIS

UniProtKB: COMM domain-containing protein 1

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Macromolecule #2: COMM domain-containing protein 2

MacromoleculeName: COMM domain-containing protein 2 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 22.776113 KDa
Recombinant expressionOrganism: Spodoptera (butterflies/moths)
SequenceString: MLLELSEEHK EHLAFLPQVD SAVVAEFGRI AVEFLRRGAN PKIYEGAARK LNVSSDTVQH GVEGLTYLLT ESSKLMISEL DFQDSVFVL GFSEELNKLL LQLYLDNRKE IRTILSELAP SLPSYHNLEW RLDVQLASRS LRQQIKPAVT IKLHLNQNGD H NTKVLQTD ...String:
MLLELSEEHK EHLAFLPQVD SAVVAEFGRI AVEFLRRGAN PKIYEGAARK LNVSSDTVQH GVEGLTYLLT ESSKLMISEL DFQDSVFVL GFSEELNKLL LQLYLDNRKE IRTILSELAP SLPSYHNLEW RLDVQLASRS LRQQIKPAVT IKLHLNQNGD H NTKVLQTD PATLLHLVQQ LEQALEEMKT NHCRRVVRNI K

UniProtKB: COMM domain-containing protein 2

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Macromolecule #3: COMM domain-containing protein 3

MacromoleculeName: COMM domain-containing protein 3 / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 22.179117 KDa
Recombinant expressionOrganism: Spodoptera (butterflies/moths)
SequenceString: MELSESVQKG FQMLADPRSF DSNAFTLLLR AAFQSLLDAQ ADEAVLDHPD LKHIDPVVLK HCHAAAATYI LEAGKHRADK STLSTYLED CKFDRERIEL FCTEYQNNKN SLEILLGSIG RSLPHITDVS WRLEYQIKTN QLHRMYRPAY LVTLSVQNTD S PSYPEISF ...String:
MELSESVQKG FQMLADPRSF DSNAFTLLLR AAFQSLLDAQ ADEAVLDHPD LKHIDPVVLK HCHAAAATYI LEAGKHRADK STLSTYLED CKFDRERIEL FCTEYQNNKN SLEILLGSIG RSLPHITDVS WRLEYQIKTN QLHRMYRPAY LVTLSVQNTD S PSYPEISF SCSMEQLQDL VGKLKDASKS LERATQL

UniProtKB: COMM domain-containing protein 3

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Macromolecule #4: COMM domain-containing protein 4

MacromoleculeName: COMM domain-containing protein 4 / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 21.790354 KDa
Recombinant expressionOrganism: Spodoptera (butterflies/moths)
SequenceString: MRFRFCGDLD CPDWVLAEIS TLAKMSSVKL RLLCSQVLKE LLGQGIDYEK ILKLTADAKF ESGDVKATVA VLSFILSSAA KHSVDGESL SSELQQLGLP KEHAASLCRC YEEKQSPLQK HLRVCSLRMN RLAGVGWRVD YTLSSSLLQS VEEPMVHLRL E VAAAPGTP ...String:
MRFRFCGDLD CPDWVLAEIS TLAKMSSVKL RLLCSQVLKE LLGQGIDYEK ILKLTADAKF ESGDVKATVA VLSFILSSAA KHSVDGESL SSELQQLGLP KEHAASLCRC YEEKQSPLQK HLRVCSLRMN RLAGVGWRVD YTLSSSLLQS VEEPMVHLRL E VAAAPGTP AQPVAMSLSA DKFQVLLAEL KQAQTLMSSL G

UniProtKB: COMM domain-containing protein 4

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Macromolecule #5: COMM domain-containing protein 5

MacromoleculeName: COMM domain-containing protein 5 / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 22.77926 KDa
Recombinant expressionOrganism: Spodoptera (butterflies/moths)
SequenceString: GRVSFLGAQL PPEVAAMARL LGDLDRSTFR KLLKFVVSSL QGEDCREAVQ RLGVSANLPE EQLGALLAGM HTLLQQALRL PPTSLKPDT FRDQLQELCI PQDLVGDLAS VVFGSQRPLL DSVAQQQGAW LPHVADFRWR VDVAISTSAL ARSLQPSVLM Q LKLSDGSA ...String:
GRVSFLGAQL PPEVAAMARL LGDLDRSTFR KLLKFVVSSL QGEDCREAVQ RLGVSANLPE EQLGALLAGM HTLLQQALRL PPTSLKPDT FRDQLQELCI PQDLVGDLAS VVFGSQRPLL DSVAQQQGAW LPHVADFRWR VDVAISTSAL ARSLQPSVLM Q LKLSDGSA YRFEVPTAKF QELRYSVALV LKEMADLEKR CERRLQD

UniProtKB: COMM domain-containing protein 5

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Macromolecule #6: COMM domain-containing protein 6

MacromoleculeName: COMM domain-containing protein 6 / type: protein_or_peptide / ID: 6 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 8.819188 KDa
Recombinant expressionOrganism: Spodoptera (butterflies/moths)
SequenceString:
LDAKSDVTNQ LVDFQWKLGM AVSSDTCRSL KYPYVAVMLK VADHSGQVKT KCFEMTIPQF QNFYRQFKEI AAVIETV

UniProtKB: COMM domain-containing protein 6

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Macromolecule #7: COMM domain-containing protein 7

MacromoleculeName: COMM domain-containing protein 7 / type: protein_or_peptide / ID: 7 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 22.561953 KDa
Recombinant expressionOrganism: Spodoptera (butterflies/moths)
SequenceString: MGRLHCTEDP VPEAVGGDMQ QLNQLGAQQF SALTEVLFHF LTEPKEVERF LAQLSEFATT NQISLGSLRS IVKSLLLVPN GALKKSLTA KQVQADFITL GLSEEKATYF SEKWKQNAPT LARWAIGQTL MINQLIDMEW KFGVTSGSSE LEKVGSIFLQ L KLVVKKGN ...String:
MGRLHCTEDP VPEAVGGDMQ QLNQLGAQQF SALTEVLFHF LTEPKEVERF LAQLSEFATT NQISLGSLRS IVKSLLLVPN GALKKSLTA KQVQADFITL GLSEEKATYF SEKWKQNAPT LARWAIGQTL MINQLIDMEW KFGVTSGSSE LEKVGSIFLQ L KLVVKKGN QTENVYIELT LPQFYSFLHE MERVRTSMEC FC

UniProtKB: COMM domain-containing protein 7

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Macromolecule #8: COMM domain-containing protein 8

MacromoleculeName: COMM domain-containing protein 8 / type: protein_or_peptide / ID: 8 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 20.629801 KDa
Recombinant expressionOrganism: Spodoptera (butterflies/moths)
SequenceString:
EGTPLWRLQK LPAELGPQLL HKIIDGICGR AYPVYQDYHT VWESEEWMHV LEDIAKFFKA IVGKNLPDEE IFQQLNQLNS LHQETIMKC VKSRKDEIKQ ALSREIVAIS SAQLQDFDWQ VKLALSSDKI AALRMPLLSL HLDVKENGEV KPYSIEMSRE E LQNLIQSL EAANKVVLQL K

UniProtKB: COMM domain-containing protein 8

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Macromolecule #9: COMM domain-containing protein 9

MacromoleculeName: COMM domain-containing protein 9 / type: protein_or_peptide / ID: 9 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 21.844117 KDa
Recombinant expressionOrganism: Spodoptera (butterflies/moths)
SequenceString: MAALTAEHFA ALQSLLKASS KDVVRQLCQE SFSSSALGLK KLLDVTCSSL SVTQEEAEEL LQALHRLTRL VAFRDLSSAE AILALFPEN FHQNLKNLLT KIILEHVSTW RTEAQANQIS LPRLVDLDWR VDIKTSSDSI SRMAVPTCLL QMKIQEDPSL C GDKPSISA ...String:
MAALTAEHFA ALQSLLKASS KDVVRQLCQE SFSSSALGLK KLLDVTCSSL SVTQEEAEEL LQALHRLTRL VAFRDLSSAE AILALFPEN FHQNLKNLLT KIILEHVSTW RTEAQANQIS LPRLVDLDWR VDIKTSSDSI SRMAVPTCLL QMKIQEDPSL C GDKPSISA VTVELSKETL DTMLDGLGRI RDQLSAVASK

UniProtKB: COMM domain-containing protein 9

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Macromolecule #10: COMM domain-containing protein 10

MacromoleculeName: COMM domain-containing protein 10 / type: protein_or_peptide / ID: 10 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 22.596881 KDa
Recombinant expressionOrganism: Spodoptera (butterflies/moths)
SequenceString: AALILRESPS MKKAVSLINA IDTGRFPRLL TRILQKLHLK AESSFSEEEE EKLQAAFSLE KQDLHLVLET ISFILEQAVY HNVKPAALQ QQLENIHLRQ DKAEAFVNTW SSMGQETVEK FRQRILAPCK LETVGWQLNL QMAHSAQAKL KSPQAVLQLG V NNEDSKSL ...String:
AALILRESPS MKKAVSLINA IDTGRFPRLL TRILQKLHLK AESSFSEEEE EKLQAAFSLE KQDLHLVLET ISFILEQAVY HNVKPAALQ QQLENIHLRQ DKAEAFVNTW SSMGQETVEK FRQRILAPCK LETVGWQLNL QMAHSAQAKL KSPQAVLQLG V NNEDSKSL EKVLVEFSHK ELFDFYNKLE TIQAQLDSLT

UniProtKB: COMM domain-containing protein 10

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

Concentration0.2 mg/mL
BufferpH: 7.2
Details: 50 mM HEPES pH7.2, 150 mM NaCl, 2mM beta-mercaptoethanol, 0.01% Triton-X100
GridModel: Quantifoil R1.2/1.3 / Material: COPPER / Support film - Material: GRAPHENE OXIDE
VitrificationCryogen name: ETHANE / Instrument: FEI VITROBOT MARK IV
DetailsHuman CCC complex cross-linked with 1 mM BS3

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: FEI FALCON IV (4k x 4k) / Number grids imaged: 2 / Number real images: 5651 / Average exposure time: 9.01 sec. / Average electron dose: 43.14 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.2 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Startup modelType of model: INSILICO MODEL / In silico model: Ab initio model generated in cryoSPARC
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.12 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC (ver. 3.3.1) / Number images used: 153104
Initial angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC (ver. 3.3.1)
Final angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC (ver. 3.3.1)
Final 3D classificationSoftware - Name: cryoSPARC (ver. 3.3.1)
FSC plot (resolution estimation)

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