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- EMDB-26513: Human L-type voltage-gated calcium channel Cav1.3 in the presence... -

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Basic information

Entry
Database: EMDB / ID: EMD-26513
TitleHuman L-type voltage-gated calcium channel Cav1.3 in the presence of cinnarizine at 3.1 Angstrom resolution
Map data
Sample
  • Complex: Cav1.3
    • Protein or peptide: Voltage-dependent L-type calcium channel subunit alpha-1D
    • Protein or peptide: Voltage-dependent calcium channel subunit alpha-2/delta-1
    • Protein or peptide: Voltage-dependent L-type calcium channel subunit beta-3
  • Ligand: 1-(diphenylmethyl)-4-[(2E)-3-phenylprop-2-en-1-yl]piperazine
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
  • Ligand: CALCIUM ION
  • Ligand: CHOLESTEROL HEMISUCCINATE
  • Ligand: 1,2-Distearoyl-sn-glycerophosphoethanolamine
KeywordsCav1.3 / Channels / Calcium Ion-Selective / TRANSPORT PROTEIN
Function / homology
Function and homology information


voltage-gated calcium channel activity involved SA node cell action potential / voltage-gated calcium channel activity involved in cardiac muscle cell action potential / membrane depolarization during SA node cell action potential / regulation of membrane repolarization during action potential / Presynaptic depolarization and calcium channel opening / regulation of potassium ion transmembrane transporter activity / positive regulation of high voltage-gated calcium channel activity / regulation of atrial cardiac muscle cell membrane repolarization / calcium ion transmembrane transport via high voltage-gated calcium channel / membrane depolarization during bundle of His cell action potential ...voltage-gated calcium channel activity involved SA node cell action potential / voltage-gated calcium channel activity involved in cardiac muscle cell action potential / membrane depolarization during SA node cell action potential / regulation of membrane repolarization during action potential / Presynaptic depolarization and calcium channel opening / regulation of potassium ion transmembrane transporter activity / positive regulation of high voltage-gated calcium channel activity / regulation of atrial cardiac muscle cell membrane repolarization / calcium ion transmembrane transport via high voltage-gated calcium channel / membrane depolarization during bundle of His cell action potential / positive regulation of adenylate cyclase activity / high voltage-gated calcium channel activity / L-type voltage-gated calcium channel complex / membrane depolarization during cardiac muscle cell action potential / positive regulation of calcium ion transport / cardiac muscle cell action potential involved in contraction / NCAM1 interactions / regulation of ventricular cardiac muscle cell membrane repolarization / calcium ion transport into cytosol / regulation of potassium ion transmembrane transport / calcium ion import / Sensory processing of sound by inner hair cells of the cochlea / regulation of calcium ion transmembrane transport via high voltage-gated calcium channel / voltage-gated calcium channel complex / ankyrin binding / neuromuscular junction development / calcium ion import across plasma membrane / neuronal dense core vesicle / alpha-actinin binding / regulation of heart rate by cardiac conduction / regulation of calcium ion transport / calcium channel regulator activity / voltage-gated calcium channel activity / sarcoplasmic reticulum / protein localization to plasma membrane / Regulation of insulin secretion / sensory perception of sound / calcium ion transmembrane transport / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / calcium channel activity / Z disc / Adrenaline,noradrenaline inhibits insulin secretion / cellular response to amyloid-beta / calcium ion transport / T cell receptor signaling pathway / chemical synaptic transmission / synapse / extracellular exosome / membrane / metal ion binding / plasma membrane / cytosol
Similarity search - Function
Voltage-dependent calcium channel, L-type, alpha-1D subunit / Voltage-dependent calcium channel, L-type, beta-3 subunit / Voltage-dependent L-type calcium channel subunit beta-3, SH3 domain / Voltage-dependent calcium channel, L-type, beta subunit / Voltage-dependent L-type calcium channel subunit beta-1-4, N-terminal A domain / Voltage gated calcium channel subunit beta domain 4Aa N terminal / Voltage-gated calcium channel subunit alpha, C-terminal / Voltage-gated calcium channel subunit alpha, C-term / Voltage-dependent calcium channel, L-type, alpha-1 subunit / VWA N-terminal ...Voltage-dependent calcium channel, L-type, alpha-1D subunit / Voltage-dependent calcium channel, L-type, beta-3 subunit / Voltage-dependent L-type calcium channel subunit beta-3, SH3 domain / Voltage-dependent calcium channel, L-type, beta subunit / Voltage-dependent L-type calcium channel subunit beta-1-4, N-terminal A domain / Voltage gated calcium channel subunit beta domain 4Aa N terminal / Voltage-gated calcium channel subunit alpha, C-terminal / Voltage-gated calcium channel subunit alpha, C-term / Voltage-dependent calcium channel, L-type, alpha-1 subunit / VWA N-terminal / Voltage-dependent calcium channel, alpha-2/delta subunit, conserved region / : / VWA N-terminal / Neuronal voltage-dependent calcium channel alpha 2acd / Voltage-dependent calcium channel, alpha-1 subunit, IQ domain / : / Voltage gated calcium channel IQ domain / Voltage gated calcium channel IQ domain / Voltage-dependent calcium channel, alpha-1 subunit / Voltage-dependent L-type calcium channel, IQ-associated domain / Voltage-dependent L-type calcium channel, IQ-associated / Guanylate kinase/L-type calcium channel beta subunit / Guanylate kinase / Guanylate kinase homologues. / von Willebrand factor type A domain / von Willebrand factor (vWF) type A domain / VWFA domain profile. / Voltage-dependent channel domain superfamily / von Willebrand factor, type A / von Willebrand factor A-like domain superfamily / SH3-like domain superfamily / Src homology 3 (SH3) domain profile. / SH3 domain / Ion transport domain / Ion transport protein / P-loop containing nucleoside triphosphate hydrolase
Similarity search - Domain/homology
Voltage-dependent L-type calcium channel subunit beta-3 / Voltage-dependent calcium channel subunit alpha-2/delta-1 / Voltage-dependent L-type calcium channel subunit alpha-1D
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.1 Å
AuthorsGao S / Yao X / Yan N
Funding support United States, 1 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)GM130762 United States
CitationJournal: Cell Res / Year: 2022
Title: Structural basis for pore blockade of human voltage-gated calcium channel Ca1.3 by motion sickness drug cinnarizine.
Authors: Xia Yao / Shuai Gao / Nieng Yan /
History
DepositionMar 26, 2022-
Header (metadata) releaseMay 11, 2022-
Map releaseMay 11, 2022-
UpdateOct 16, 2024-
Current statusOct 16, 2024Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_26513.png

Downloads & links

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Map

FileDownload / File: emd_26513.map.gz / Format: CCP4 / Size: 83.7 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.11 Å/pix.
x 280 pix.
= 311.92 Å		1.11 Å/pix.
x 280 pix.
= 311.92 Å		1.11 Å/pix.
x 280 pix.
= 311.92 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.114 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.03
Minimum - Maximum-0.10781965 - 0.18065308
Average (Standard dev.)-0.0000026248565 (±0.005527882)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions280280280
Spacing280280280
CellA=B=C: 311.91998 Å
α=β=γ: 90.0 °

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Supplemental data

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Sample components

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Entire : Cav1.3

EntireName: Cav1.3
Components
  • Complex: Cav1.3
    • Protein or peptide: Voltage-dependent L-type calcium channel subunit alpha-1D
    • Protein or peptide: Voltage-dependent calcium channel subunit alpha-2/delta-1
    • Protein or peptide: Voltage-dependent L-type calcium channel subunit beta-3
  • Ligand: 1-(diphenylmethyl)-4-[(2E)-3-phenylprop-2-en-1-yl]piperazine
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
  • Ligand: CALCIUM ION
  • Ligand: CHOLESTEROL HEMISUCCINATE
  • Ligand: 1,2-Distearoyl-sn-glycerophosphoethanolamine

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Supramolecule #1: Cav1.3

SupramoleculeName: Cav1.3 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: Voltage-dependent L-type calcium channel subunit alpha-1D

MacromoleculeName: Voltage-dependent L-type calcium channel subunit alpha-1D
type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 245.417734 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MMMMMMMKKM QHQRQQQADH ANEANYARGT RLPLSGEGPT SQPNSSKQTV LSWQAAIDAA RQAKAAQTMS TSAPPPVGSL SQRKRQQYA KSKKQGNSSN SRPARALFCL SLNNPIRRAC ISIVEWKPFD IFILLAIFAN CVALAIYIPF PEDDSNSTNH N LEKVEYAF ...String:
MMMMMMMKKM QHQRQQQADH ANEANYARGT RLPLSGEGPT SQPNSSKQTV LSWQAAIDAA RQAKAAQTMS TSAPPPVGSL SQRKRQQYA KSKKQGNSSN SRPARALFCL SLNNPIRRAC ISIVEWKPFD IFILLAIFAN CVALAIYIPF PEDDSNSTNH N LEKVEYAF LIIFTVETFL KIIAYGLLLH PNAYVRNGWN LLDFVIVIVG LFSVILEQLT KETEGGNHSS GKSGGFDVKA LR AFRVLRP LRLVSGVPSL QVVLNSIIKA MVPLLHIALL VLFVIIIYAI IGLELFIGKM HKTCFFADSD IVAEEDPAPC AFS GNGRQC TANGTECRSG WVGPNGGITN FDNFAFAMLT VFQCITMEGW TDVLYWMNDA MGFELPWVYF VSLVIFGSFF VLNL VLGVL SGEFSKEREK AKARGDFQKL REKQQLEEDL KGYLDWITQA EDIDPENEEE GGEEGKRNTS MPTSETESVN TENVS GEGE NRGCCGSLCQ AISKSKLSRR WRRWNRFNRR RCRAAVKSVT FYWLVIVLVF LNTLTISSEH YNQPDWLTQI QDIANK VLL ALFTCEMLVK MYSLGLQAYF VSLFNRFDCF VVCGGITETI LVELEIMSPL GISVFRCVRL LRIFKVTRHW TSLSNLV AS LLNSMKSIAS LLLLLFLFII IFSLLGMQLF GGKFNFDETQ TKRSTFDNFP QALLTVFQIL TGEDWNAVMY DGIMAYGG P SSSGMIVCIY FIILFICGNY ILLNVFLAIA VDNLADAESL NTAQKEEAEE KERKKIARKE SLENKKNNKP EVNQIANSD NKVTIDDYRE EDEDKDPYPP CDVPVGEEEE EEEEDEPEVP AGPRPRRISE LNMKEKIAPI PEGSAFFILS KTNPIRVGCH KLINHHIFT NLILVFIMLS SAALAAEDPI RSHSFRNTIL GYFDYAFTAI FTVEILLKMT TFGAFLHKGA FCRNYFNLLD M LVVGVSLV SFGIQSSAIS VVKILRVLRV LRPLRAINRA KGLKHVVQCV FVAIRTIGNI MIVTTLLQFM FACIGVQLFK GK FYRCTDE AKSNPEECRG LFILYKDGDV DSPVVRERIW QNSDFNFDNV LSAMMALFTV STFEGWPALL YKAIDSNGEN IGP IYNHRV EISIFFIIYI IIVAFFMMNI FVGFVIVTFQ EQGEKEYKNC ELDKNQRQCV EYALKARPLR RYIPKNPYQY KFWY VVNSS PFEYMMFVLI MLNTLCLAMQ HYEQSKMFND AMDILNMVFT GVFTVEMVLK VIAFKPKGYF SDAWNTFDSL IVIGS IIDV ALSEADPTES ENVPVPTATP GNSEESNRIS ITFFRLFRVM RLVKLLSRGE GIRTLLWTFI KSFQALPYVA LLIAML FFI YAVIGMQMFG KVAMRDNNQI NRNNNFQTFP QAVLLLFRCA TGEAWQEIML ACLPGKLCDP ESDYNPGEEY TCGSNFA IV YFISFYMLCA FLIINLFVAV IMDNFDYLTR DWSILGPHHL DEFKRIWSEY DPEAKGRIKH LDVVTLLRRI QPPLGFGK L CPHRVACKRL VAMNMPLNSD GTVMFNATLF ALVRTALKIK TEGNLEQANE ELRAVIKKIW KKTSMKLLDQ VVPPAGDDE VTVGKFYATF LIQDYFRKFK KRKEQGLVGK YPAKNTTIAL QAGLRTLHDI GPEIRRAISC DLQDDEPEET KREEEDDVFK RNGALLGNH VNHVNSDRRD SLQQTNTTHR PLHVQRPSIP PASDTEKPLF PPAGNSVCHN HHNHNSIGKQ VPTSTNANLN N ANMSKAAH GKRPSIGNLE HVSENGHHSS HKHDREPQRR SSVKRTRYYE TYIRSDSGDE QLPTICREDP EIHGYFRDPH CL GEQEYFS SEECYEDDSS PTWSRQNYGY YSRYPGRNID SERPRGYHHP QGFLEDDDSP VCYDSRRSPR RRLLPPTPAS HRR SSFNFE CLRRQSSQEE VPSSPIFPHR TALPLHLMQQ QIMAVAGLDS SKAQKYSPSH STRSWATPPA TPPYRDWTPC YTPL IQVEQ SEALDQVNGS LPSLHRSSWY TDEPDISYRT FTPASLTVPS SFRNKNSDKQ RSADSLVEAV LISEGLGRYA RDPKF VSAT KHEIADACDL TIDEMESAAS TLLNGNVRPR ANGDVGPLSH RQDYELQDFG PGYSDEEPDP GRDEEDLADE MICITT L

UniProtKB: Voltage-dependent L-type calcium channel subunit alpha-1D

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Macromolecule #2: Voltage-dependent calcium channel subunit alpha-2/delta-1

MacromoleculeName: Voltage-dependent calcium channel subunit alpha-2/delta-1
type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 124.692469 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MAAGCLLALT LTLFQSLLIG PSSEEPFPSA VTIKSWVDKM QEDLVTLAKT ASGVNQLVDI YEKYQDLYTV EPNNARQLVE IAARDIEKL LSNRSKALVR LALEAEKVQA AHQWREDFAS NEVVYYNAKD DLDPEKNDSE PGSQRIKPVF IEDANFGRQI S YQHAAVHI ...String:
MAAGCLLALT LTLFQSLLIG PSSEEPFPSA VTIKSWVDKM QEDLVTLAKT ASGVNQLVDI YEKYQDLYTV EPNNARQLVE IAARDIEKL LSNRSKALVR LALEAEKVQA AHQWREDFAS NEVVYYNAKD DLDPEKNDSE PGSQRIKPVF IEDANFGRQI S YQHAAVHI PTDIYEGSTI VLNELNWTSA LDEVFKKNRE EDPSLLWQVF GSATGLARYY PASPWVDNSR TPNKIDLYDV RR RPWYIQG AASPKDMLIL VDVSGSVSGL TLKLIRTSVS EMLETLSDDD FVNVASFNSN AQDVSCFQHL VQANVRNKKV LKD AVNNIT AKGITDYKKG FSFAFEQLLN YNVSRANCNK IIMLFTDGGE ERAQEIFNKY NKDKKVRVFT FSVGQHNYDR GPIQ WMACE NKGYYYEIPS IGAIRINTQE YLDVLGRPMV LAGDKAKQVQ WTNVYLDALE LGLVITGTLP VFNITGQFEN KTNLK NQLI LGVMGVDVSL EDIKRLTPRF TLCPNGYYFA IDPNGYVLLH PNLQPKPIGV GIPTINLRKR RPNIQNPKSQ EPVTLD FLD AELENDIKVE IRNKMIDGES GEKTFRTLVK SQDERYIDKG NRTYTWTPVN GTDYSLALVL PTYSFYYIKA KLEETIT QA RYSETLKPDN FEESGYTFIA PRDYCNDLKI SDNNTEFLLN FNEFIDRKTP NNPSCNADLI NRVLLDAGFT NELVQNYW S KQKNIKGVKA RFVVTDGGIT RVYPKEAGEN WQENPETYED SFYKRSLDND NYVFTAPYFN KSGPGAYESG IMVSKAVEI YIQGKLLKPA VVGIKIDVNS WIENFTKTSI RDPCAGPVCD CKRNSDVMDC VILDDGGFLL MANHDDYTNQ IGRFFGEIDP SLMRHLVNI SVYAFNKSYD YQSVCEPGAA PKQGAGHRSA YVPSVADILQ IGWWATAAAW SILQQFLLSL TFPRLLEAVE M EDDDFTAS LSKQSCITEQ TQYFFDNDSK SFSGVLDCGN CSRIFHGEKL MNTNLIFIMV ESKGTCPCDT RLLIQAEQTS DG PNPCDMV KQPRYRKGPD VCFDNNVLED YTDCGGVSGL NPSLWYIIGI QFLLLWLVSG STHRLL

UniProtKB: Voltage-dependent calcium channel subunit alpha-2/delta-1

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Macromolecule #3: Voltage-dependent L-type calcium channel subunit beta-3

MacromoleculeName: Voltage-dependent L-type calcium channel subunit beta-3
type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 54.607852 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MYDDSYVPGF EDSEAGSADS YTSRPSLDSD VSLEEDRESA RREVESQAQQ QLERAKHKPV AFAVRTNVSY CGVLDEECPV QGSGVNFEA KDFLHIKEKY SNDWWIGRLV KEGGDIAFIP SPQRLESIRL KQEQKARRSG NPSSLSDIGN RRSPPPSLAK Q KQKQAEHV ...String:
MYDDSYVPGF EDSEAGSADS YTSRPSLDSD VSLEEDRESA RREVESQAQQ QLERAKHKPV AFAVRTNVSY CGVLDEECPV QGSGVNFEA KDFLHIKEKY SNDWWIGRLV KEGGDIAFIP SPQRLESIRL KQEQKARRSG NPSSLSDIGN RRSPPPSLAK Q KQKQAEHV PPYDVVPSMR PVVLVGPSLK GYEVTDMMQK ALFDFLKHRF DGRISITRVT ADLSLAKRSV LNNPGKRTII ER SSARSSI AEVQSEIERI FELAKSLQLV VLDADTINHP AQLAKTSLAP IIVFVKVSSP KVLQRLIRSR GKSQMKHLTV QMM AYDKLV QCPPESFDVI LDENQLEDAC EHLAEYLEVY WRATHHPAPG PGLLGPPSAI PGLQNQQLLG ERGEEHSPLE RDSL MPSDE ASESSRQAWT GSSQRSSRHL EEDYADAYQD LYQPHRQHTS GLPSANGHDP QDRLLAQDSE HNHSDRNWQR NRPWP KDSY

UniProtKB: Voltage-dependent L-type calcium channel subunit beta-3

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Macromolecule #7: 1-(diphenylmethyl)-4-[(2E)-3-phenylprop-2-en-1-yl]piperazine

MacromoleculeName: 1-(diphenylmethyl)-4-[(2E)-3-phenylprop-2-en-1-yl]piperazine
type: ligand / ID: 7 / Number of copies: 1 / Formula: N90
Molecular weightTheoretical: 368.514 Da
Chemical component information

ChemComp-N90:
1-(diphenylmethyl)-4-[(2E)-3-phenylprop-2-en-1-yl]piperazine / chemotherapy, channel blocker*YM

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Macromolecule #8: 2-acetamido-2-deoxy-beta-D-glucopyranose

MacromoleculeName: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 8 / Number of copies: 3 / Formula: NAG
Molecular weightTheoretical: 221.208 Da
Chemical component information

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

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Macromolecule #9: CALCIUM ION

MacromoleculeName: CALCIUM ION / type: ligand / ID: 9 / Number of copies: 2 / Formula: CA
Molecular weightTheoretical: 40.078 Da

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Macromolecule #10: CHOLESTEROL HEMISUCCINATE

MacromoleculeName: CHOLESTEROL HEMISUCCINATE / type: ligand / ID: 10 / Number of copies: 1 / Formula: Y01
Molecular weightTheoretical: 486.726 Da
Chemical component information

ChemComp-Y01:
CHOLESTEROL HEMISUCCINATE

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Macromolecule #11: 1,2-Distearoyl-sn-glycerophosphoethanolamine

MacromoleculeName: 1,2-Distearoyl-sn-glycerophosphoethanolamine / type: ligand / ID: 11 / Number of copies: 1 / Formula: 3PE
Molecular weightTheoretical: 748.065 Da
Chemical component information

ChemComp-3PE:
1,2-Distearoyl-sn-glycerophosphoethanolamine / phospholipid*YM

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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

BufferpH: 7.4
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 281 K

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 50.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.1 µm / Nominal defocus min: 1.9000000000000001 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Startup modelType of model: OTHER
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.1 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 51625
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD

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