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- EMDB-66174: GRM5-Gi Complex Structure -

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Basic information

Entry
Database: EMDB / ID: EMD-66174
TitleGRM5-Gi Complex Structure
Map data
Sample
  • Complex: GRM5-Gi complex
    • Protein or peptide: Metabotropic glutamate receptor 5
    • Protein or peptide: Guanine nucleotide-binding protein G(i) subunit alpha-1
    • Protein or peptide: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
    • Protein or peptide: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
    • Protein or peptide: scFv16
  • Ligand: 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide
  • Ligand: GAMMA-L-GLUTAMIC ACID
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
  • Ligand: CHLORIDE ION
  • Ligand: CHOLESTEROL
KeywordsReceptor complex / MEMBRANE PROTEIN
Function / homology
Function and homology information


A2A adenosine receptor binding / sensory perception of hot stimulus / negative regulation of dendritic spine morphogenesis / : / G protein-coupled receptor activity involved in regulation of postsynaptic membrane potential / adenylate cyclase inhibiting G protein-coupled glutamate receptor activity / operant conditioning / protein localization to nuclear inner membrane / phospholipase C-activating G protein-coupled glutamate receptor signaling pathway / positive regulation of cellular response to hypoxia ...A2A adenosine receptor binding / sensory perception of hot stimulus / negative regulation of dendritic spine morphogenesis / : / G protein-coupled receptor activity involved in regulation of postsynaptic membrane potential / adenylate cyclase inhibiting G protein-coupled glutamate receptor activity / operant conditioning / protein localization to nuclear inner membrane / phospholipase C-activating G protein-coupled glutamate receptor signaling pathway / positive regulation of cellular response to hypoxia / positive regulation of long-term neuronal synaptic plasticity / positive regulation of sensory perception of pain / negative regulation of excitatory postsynaptic potential / positive regulation of dopamine secretion / desensitization of G protein-coupled receptor signaling pathway / G protein-coupled glutamate receptor signaling pathway / positive regulation of neural precursor cell proliferation / Class C/3 (Metabotropic glutamate/pheromone receptors) / nuclear inner membrane / glutamate receptor activity / Neurexins and neuroligins / astrocyte projection / response to corticosterone / response to morphine / temperature homeostasis / protein tyrosine kinase activator activity / conditioned place preference / regulation of synaptic transmission, glutamatergic / adenylate cyclase inhibitor activity / positive regulation of protein localization to cell cortex / T cell migration / regulation of long-term synaptic depression / positive regulation of relaxation of smooth muscle / Adenylate cyclase inhibitory pathway / D2 dopamine receptor binding / adenylate cyclase-inhibiting serotonin receptor signaling pathway / G protein-coupled serotonin receptor binding / positive regulation of calcium-mediated signaling / cellular response to forskolin / protein tyrosine kinase binding / regulation of mitotic spindle organization / chemokine-mediated signaling pathway / dendritic shaft / response to amphetamine / Regulation of insulin secretion / neuropeptide signaling pathway / response to prostaglandin E / locomotory behavior / positive regulation of cholesterol biosynthetic process / negative regulation of insulin secretion / synapse organization / G protein-coupled receptor binding / postsynaptic density membrane / response to peptide hormone / G protein-coupled receptor activity / Schaffer collateral - CA1 synapse / cognition / cellular response to amyloid-beta / G-protein beta/gamma-subunit complex binding / centriolar satellite / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G protein-coupled acetylcholine receptor signaling pathway / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G-protein activation / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / Prostacyclin signalling through prostacyclin receptor / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / G beta:gamma signalling through BTK / photoreceptor disc membrane / ADP signalling through P2Y purinoceptor 12 / Sensory perception of sweet, bitter, and umami (glutamate) taste / Glucagon-type ligand receptors / GDP binding / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / G alpha (z) signalling events / cellular response to catecholamine stimulus / ADP signalling through P2Y purinoceptor 1 / ADORA2B mediated anti-inflammatory cytokines production / G beta:gamma signalling through PI3Kgamma / adenylate cyclase-activating dopamine receptor signaling pathway / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GPER1 signaling / cellular response to prostaglandin E stimulus / heterotrimeric G-protein complex / G alpha (12/13) signalling events / Inactivation, recovery and regulation of the phototransduction cascade / G-protein beta-subunit binding / extracellular vesicle / sensory perception of taste / sperm principal piece
Similarity search - Function
GPCR, family 3, metabotropic glutamate receptor 5 / Metabotropic glutamate receptor, Homer-binding domain / Homer-binding domain of metabotropic glutamate receptor / GluR_Homer-bdg / GPCR, family 3, metabotropic glutamate receptor / : / G-protein coupled receptors family 3 signature 1. / G-protein coupled receptors family 3 signature 3. / G-protein coupled receptors family 3 signature 2. / GPCR, family 3, nine cysteines domain ...GPCR, family 3, metabotropic glutamate receptor 5 / Metabotropic glutamate receptor, Homer-binding domain / Homer-binding domain of metabotropic glutamate receptor / GluR_Homer-bdg / GPCR, family 3, metabotropic glutamate receptor / : / G-protein coupled receptors family 3 signature 1. / G-protein coupled receptors family 3 signature 3. / G-protein coupled receptors family 3 signature 2. / GPCR, family 3, nine cysteines domain / GPCR, family 3, nine cysteines domain superfamily / Nine Cysteines Domain of family 3 GPCR / GPCR, family 3, conserved site / GPCR, family 3 / G-protein coupled receptors family 3 profile. / GPCR family 3, C-terminal / 7 transmembrane sweet-taste receptor of 3 GCPR / G-protein alpha subunit, group I / Receptor, ligand binding region / Receptor family ligand binding region / Periplasmic binding protein-like I / G protein alpha subunit, helical insertion / G protein alpha subunit / Guanine nucleotide binding protein (G-protein), alpha subunit / G-protein alpha subunit / G-alpha domain profile. / G-protein, gamma subunit / G-protein gamma subunit domain profile. / G-protein gamma-like domain / G-protein gamma-like domain superfamily / GGL domain / G protein gamma subunit-like motifs / GGL domain / G protein beta WD-40 repeat protein / Guanine nucleotide-binding protein, beta subunit / G-protein, beta subunit / G-protein beta WD-40 repeat / WD40 repeat, conserved site / Trp-Asp (WD) repeats signature. / Trp-Asp (WD) repeats profile. / Trp-Asp (WD) repeats circular profile. / WD40 repeats / WD40 repeat / WD40-repeat-containing domain superfamily / WD40/YVTN repeat-like-containing domain superfamily / P-loop containing nucleoside triphosphate hydrolase
Similarity search - Domain/homology
Metabotropic glutamate receptor 5 / Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 / Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 / Guanine nucleotide-binding protein G(i) subunit alpha-1
Similarity search - Component
Biological speciesHomo sapiens (human) / Mus musculus (house mouse)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.7 Å
AuthorsLu Y / Wen TL / Shen YQ / Yang X
Funding support China, 1 items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC) China
CitationJournal: To Be Published
Title: GRM5-Gi Complex Structure
Authors: Lu Y / Wen TL / Shen YQ / Yang X
History
DepositionSep 11, 2025-
Header (metadata) releaseMay 27, 2026-
Map releaseMay 27, 2026-
UpdateMay 27, 2026-
Current statusMay 27, 2026Processing site: PDBc / Status: Released

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Structure visualization

Supplemental images

Downloads & links

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Map

FileDownload / File: emd_66174.map.gz / Format: CCP4 / Size: 216 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.93 Å/pix.
x 384 pix.
= 357.12 Å
0.93 Å/pix.
x 384 pix.
= 357.12 Å
0.93 Å/pix.
x 384 pix.
= 357.12 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.93 Å
Density
Contour LevelBy AUTHOR: 0.0027
Minimum - Maximum-0.0037704806 - 0.029757764
Average (Standard dev.)0.000033516593 (±0.0005037931)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions384384384
Spacing384384384
CellA=B=C: 357.12 Å
α=β=γ: 90.0 °

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Supplemental data

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Sample components

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Entire : GRM5-Gi complex

EntireName: GRM5-Gi complex
Components
  • Complex: GRM5-Gi complex
    • Protein or peptide: Metabotropic glutamate receptor 5
    • Protein or peptide: Guanine nucleotide-binding protein G(i) subunit alpha-1
    • Protein or peptide: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
    • Protein or peptide: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
    • Protein or peptide: scFv16
  • Ligand: 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide
  • Ligand: GAMMA-L-GLUTAMIC ACID
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
  • Ligand: CHLORIDE ION
  • Ligand: CHOLESTEROL

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Supramolecule #1: GRM5-Gi complex

SupramoleculeName: GRM5-Gi complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#5
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 300 KDa

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Macromolecule #1: Metabotropic glutamate receptor 5

MacromoleculeName: Metabotropic glutamate receptor 5 / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 95.310016 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString: MWSHPQFEKG GGSGGGSGGS AWSHPQFEKG SQSSERRVVA HMPGDIIIGA LFSVHHQPTV DKVHERKCGA VREQYGIQRV EAMLHTLER INSDPTLLPN ITLGCEIRDS CWHSAVALEQ SIEFIRDSLI SSEEEEGLVR CVDGSSSSFR SKKPIVGVIG P GSSSVAIQ ...String:
MWSHPQFEKG GGSGGGSGGS AWSHPQFEKG SQSSERRVVA HMPGDIIIGA LFSVHHQPTV DKVHERKCGA VREQYGIQRV EAMLHTLER INSDPTLLPN ITLGCEIRDS CWHSAVALEQ SIEFIRDSLI SSEEEEGLVR CVDGSSSSFR SKKPIVGVIG P GSSSVAIQ VQNLLQLFNI PQIAYSATSM DLSDKTLFKY FMRVVPSDAQ QARAMVDIVK RYNWTYVSAV HTEGNYGESG ME AFKDMSA KEGICIAHSY KIYSNAGEQS FDKLLKKLTS HLPKARVVAC FCEGMTVRGL LMAMRRLGLA GEFLLLGSDG WAD RYDVTD GYQREAVGGI TIKLQSPDVK WFDDYYLKLR PETNHRNPWF QEFWQHRFQC RLEGFPQENS KYNKTCNSSL TLKT HHVQD SKMGFVINAI YSMAYGLHNM QMSLCPGYAG LCDAMKPIDG RKLLESLMKT NFTGVSGDTI LFDENGDSPG RYEIM NFKE MGKDYFDYIN VGSWDNGELK MDDDEVWSKK SNIIRSVCSE PCEKGQIKVI RKGEVSCCWT CTPCKENEYV FDEYTC KAC QLGSWPTDDL TGCDLIPVQY LRWGDPEPIA AVVFACLGLL ATLFVTVVFI IYRDTPVVKS SSRELCYIIL AGICLGY LC TFCLIAKPKQ IYCYLQRIGI GLSPAMSYSA LVTKTNRIAR ILAGSKKKIC TKKPRFMSAC AQLVIAFILI CIQLGIIV A LFIMEPPDIM HDYPSIREVY LICNTTNLGV VTPLGYNGLL ILSCTFYAFK TRNVPANFNE AKYIAFTMYT TCIIWLAFV PIYFGSNYKI ITMCFSVSLS ATVALGCMFV PKVYIILAKP ERNVRSAFTT

UniProtKB: Metabotropic glutamate receptor 5

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Macromolecule #2: Guanine nucleotide-binding protein G(i) subunit alpha-1

MacromoleculeName: Guanine nucleotide-binding protein G(i) subunit alpha-1
type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
EC number: Hydrolases; Acting on acid anhydrides; Acting on GTP to facilitate cellular and subcellular movement
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 40.414047 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString: MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKNTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI ...String:
MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKNTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI PTQQDVLRTR VKTTGIVETH FTFKDLHFKM FDVGAQRSER KKWIHCFEGV TAIIFCVALS DYDLVLAEDE EM NRMHASM KLFDSICNNK WFTDTSIILF LNKKDLFEEK IKKSPLTICY PEYAGSNTYE EAAAYIQCQF EDLNKRKDTK EIY THFTCS TDTKNVQFVF DAVTDVIIKN NLKDCGLF

UniProtKB: Guanine nucleotide-binding protein G(i) subunit alpha-1

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Macromolecule #3: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1

MacromoleculeName: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 37.41693 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString: MSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKLI IWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR EGNVRVSREL AGHTGYLSCC RFLDDNQIVT S SGDTTCAL ...String:
MSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKLI IWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR EGNVRVSREL AGHTGYLSCC RFLDDNQIVT S SGDTTCAL WDIETGQQTT TFTGHTGDVM SLSLAPDTRL FVSGACDASA KLWDVREGMC RQTFTGHESD INAICFFPNG NA FATGSDD ATCRLFDLRA DQELMTYSHD NIICGITSVS FSKSGRLLLA GYDDFNCNVW DALKADRAGV LAGHDNRVSC LGV TDDGMA VATGSWDSFL KIWN

UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1

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Macromolecule #4: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2

MacromoleculeName: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 8.506765 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString:
MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFCAI LGSAGSAGSA

UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2

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Macromolecule #5: scFv16

MacromoleculeName: scFv16 / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Mus musculus (house mouse)
Molecular weightTheoretical: 27.720795 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: DVQLVESGGG LVQPGGSRKL SCSASGFAFS SFGMHWVRQA PEKGLEWVAY ISSGSGTIYY ADTVKGRFTI SRDDPKNTLF LQMTSLRSE DTAMYYCVRS IYYYGSSPFD FWGQGTTLTV SSGGGGSGGG GSGGGGSDIV MTQATSSVPV TPGESVSISC R SSKSLLHS ...String:
DVQLVESGGG LVQPGGSRKL SCSASGFAFS SFGMHWVRQA PEKGLEWVAY ISSGSGTIYY ADTVKGRFTI SRDDPKNTLF LQMTSLRSE DTAMYYCVRS IYYYGSSPFD FWGQGTTLTV SSGGGGSGGG GSGGGGSDIV MTQATSSVPV TPGESVSISC R SSKSLLHS NGNTYLYWFL QRPGQSPQLL IYRMSNLASG VPDRFSGSGS GTAFTLTISR LEAEDVGVYY CMQHLEYPLT FG AGTKLEL KAAAASSEDL YFQ

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Macromolecule #6: 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide

MacromoleculeName: 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide / type: ligand / ID: 6 / Number of copies: 1 / Formula: YKU
Molecular weightTheoretical: 364.399 Da
Chemical component information

ChemComp-YKU:
3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide / antipsychotic*YM

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Macromolecule #7: GAMMA-L-GLUTAMIC ACID

MacromoleculeName: GAMMA-L-GLUTAMIC ACID / type: ligand / ID: 7 / Number of copies: 2 / Formula: GGL
Molecular weightTheoretical: 147.129 Da
Chemical component information

ChemComp-GGL:
GAMMA-L-GLUTAMIC ACID

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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: 8 / 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: CHLORIDE ION

MacromoleculeName: CHLORIDE ION / type: ligand / ID: 9 / Number of copies: 2 / Formula: CL
Molecular weightTheoretical: 35.453 Da

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Macromolecule #10: CHOLESTEROL

MacromoleculeName: CHOLESTEROL / type: ligand / ID: 10 / Number of copies: 8 / Formula: CLR
Molecular weightTheoretical: 386.654 Da
Chemical component information

ChemComp-CLR:
CHOLESTEROL

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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

Concentration10 mg/mL
BufferpH: 7.2
VitrificationCryogen name: ETHANE / Chamber humidity: 100 %

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Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: FEI FALCON IV (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: 19.0 µm / Nominal defocus min: 6.0 µm
Sample stageSpecimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

CTF correctionSoftware - Name: CTFFIND (ver. 4) / Type: NONE
Startup modelType of model: OTHER / Details: CryoSPARC Ab initio
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.7 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION (ver. 5) / Number images used: 161016
Initial angle assignmentType: ANGULAR RECONSTITUTION
Final angle assignmentType: ANGULAR RECONSTITUTION

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