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- EMDB-44539: Cryo-EM structure of human monoclonal antibody C74 targeting PFD1... -

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Basic information

Entry
Database: EMDB / ID: EMD-44539
TitleCryo-EM structure of human monoclonal antibody C74 targeting PFD1235w (CIDRa1.6) PfEMP1
Map data
Sample
  • Cell: Complex of human monoclonal C74 with PfEMP1 PFD1235w N-terminal domain complex
    • Protein or peptide: C74 heavy chain
    • Protein or peptide: C74 kappa chain
    • Protein or peptide: Erythrocyte membrane protein 1, PfEMP1
KeywordsAntibody / Plasmodium / Monoclonal / Neutralizing / IMMUNE SYSTEM
Function / homology
Function and homology information


symbiont-mediated perturbation of host erythrocyte aggregation / infected host cell surface knob / antigenic variation / adhesion of symbiont to microvasculature / cell adhesion molecule binding / cell-cell adhesion / host cell surface receptor binding / host cell plasma membrane / membrane
Similarity search - Function
: / PfEMP1 protein, CIDRalpha1 domain / Plasmodium falciparum erythrocyte membrane protein-1, N-terminal segment / N-terminal segments of PfEMP1 / Cysteine-rich interdomain region 1 gamma / Cysteine-Rich Interdomain Region 1 gamma / Duffy-binding-like domain, C-terminal subdomain / Duffy-binding-like domain / PFEMP1 DBL domain / Plasmodium falciparum erythrocyte membrane protein 1, acidic terminal segment superfamily ...: / PfEMP1 protein, CIDRalpha1 domain / Plasmodium falciparum erythrocyte membrane protein-1, N-terminal segment / N-terminal segments of PfEMP1 / Cysteine-rich interdomain region 1 gamma / Cysteine-Rich Interdomain Region 1 gamma / Duffy-binding-like domain, C-terminal subdomain / Duffy-binding-like domain / PFEMP1 DBL domain / Plasmodium falciparum erythrocyte membrane protein 1, acidic terminal segment superfamily / Plasmodium falciparum erythrocyte membrane protein 1, acidic terminal segment / acidic terminal segments, variant surface antigen of PfEMP1 / Duffy-antigen binding / Duffy-antigen binding superfamily / Duffy binding domain
Similarity search - Domain/homology
Erythrocyte membrane protein 1, PfEMP1
Similarity search - Component
Biological speciesPlasmodium falciparum 3D7 (eukaryote) / Homo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.1 Å
AuthorsRaghavan SSR / Ward AB
Funding support United States, Denmark, 2 items
OrganizationGrant numberCountry
Bill & Melinda Gates Foundation United States
Lundbeckfonden Denmark
CitationJournal: To Be Published
Title: Cryo-EM structure of human monoclonal C74 targeting CIDRa1.6 PfEMP1 malarial protein
Authors: Raghavan SSR / Ward AB
History
DepositionApr 19, 2024-
Header (metadata) releaseOct 2, 2024-
Map releaseOct 2, 2024-
UpdateNov 6, 2024-
Current statusNov 6, 2024Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_44539.png

Downloads & links

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Map

FileDownload / File: emd_44539.map.gz / Format: CCP4 / Size: 178 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.73 Å/pix.
x 360 pix.
= 261. Å		0.73 Å/pix.
x 360 pix.
= 261. Å		0.73 Å/pix.
x 360 pix.
= 261. Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.725 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.085
Minimum - Maximum-0.43072158 - 0.6839186
Average (Standard dev.)0.000057604062 (±0.008648803)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions360360360
Spacing360360360
CellA=B=C: 261.0 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #2

Fileemd_44539_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: #1

Fileemd_44539_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : Complex of human monoclonal C74 with PfEMP1 PFD1235w N-terminal d...

EntireName: Complex of human monoclonal C74 with PfEMP1 PFD1235w N-terminal domain complex
Components
  • Cell: Complex of human monoclonal C74 with PfEMP1 PFD1235w N-terminal domain complex
    • Protein or peptide: C74 heavy chain
    • Protein or peptide: C74 kappa chain
    • Protein or peptide: Erythrocyte membrane protein 1, PfEMP1

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Supramolecule #1: Complex of human monoclonal C74 with PfEMP1 PFD1235w N-terminal d...

SupramoleculeName: Complex of human monoclonal C74 with PfEMP1 PFD1235w N-terminal domain complex
type: cell / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Plasmodium falciparum 3D7 (eukaryote)

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Macromolecule #1: C74 heavy chain

MacromoleculeName: C74 heavy chain / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 13.441013 KDa
Recombinant expressionOrganism: Cricetulus griseus (Chinese hamster)
SequenceString:
EVQLVQSGGA LVRPGGSLRL SCAASGFDFS DFEMNWVRQA PGKGLEWISY ISKISAASFY ADSVEGRFTI SRDNTKNLLW LEMTSLRDE DTAVYYCARD LPGYLERVFD LWGQGTLVSV SS

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Macromolecule #2: C74 kappa chain

MacromoleculeName: C74 kappa chain / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 12.178488 KDa
Recombinant expressionOrganism: Cricetulus griseus (Chinese hamster)
SequenceString:
EIVLTQSPAT LSLSPGEDAT LSCRASQSVG SALAWYQHRP GQSPRLLIYD ASTRATGIPA RFSGSGSGTE FTLTVSSLTS EDFAVYYCQ EYKNSVPPTW TFGQGTKVEI KRTV

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Macromolecule #3: Erythrocyte membrane protein 1, PfEMP1

MacromoleculeName: Erythrocyte membrane protein 1, PfEMP1 / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Plasmodium falciparum 3D7 (eukaryote)
Molecular weightTheoretical: 85.069266 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString: MGNASSSEGE AKTPSLTESH NSARNILEGY AESIKEQASK DAKIHGHHLK GDLAKAVFRH PFSAYRPNYG NPCELDYRFH TNVWHRNAE DRNPCLFSRA KRFSNEGEAE CNGGIITGNK GECGACAPYR RRHICDYNLH HINENNIRNT HDLLGNLLVM A RSEGESIV ...String:
MGNASSSEGE AKTPSLTESH NSARNILEGY AESIKEQASK DAKIHGHHLK GDLAKAVFRH PFSAYRPNYG NPCELDYRFH TNVWHRNAE DRNPCLFSRA KRFSNEGEAE CNGGIITGNK GECGACAPYR RRHICDYNLH HINENNIRNT HDLLGNLLVM A RSEGESIV KSHEYTGYGI YKSGICTSLA RSFADIGDII RGKDLYRRDS RTDKLEENLR KIFANIYKEL KNGKKWAEAK EY YQDDGTG NYYKLREAWW ALNRKDVWKA LTCSAPRDAQ YFIKSSVRDQ TFSNDYCGHG EHEVLTNLDY VPQFLRWFEE WAE EFCRIK KIKLGKVKEA CRDDSKKLYC SHNGYDCTKT IRNKDILSDN PKCTGCSVKC KVYELWLRNQ RNEFEKQKKK YYKE IQTYT SKDAKTDSNI NNEYYKEFYD KLKNEGYETL NKFIKLLNEG RYCKEKISGE RNIDFTMTGD KDAFYRSDYC QICPE CGVQ CSGTTCTPKK VIHPNCKDKE TYEPGDAKTT DITVLYSGDE EGDIAQKLQD FCNDKNKEND ENYEKWQCYY KSSEIN KCQ MTPSSHKVPK HGYIMSFYAF FDLWVKNLLI DSINWKNDLT NCINNTNVTD CKNDCNTNCK CFENWAKTKE NEWKKVK TI YKNENGNTNN YYKKLNNHFQ GYFFHVMKEL NKEEKWYKLM EDLKEKIDSS NLKNGTKDSE GAIKVLFDHL KDIAERCI D NNSKDSC

UniProtKB: Erythrocyte membrane protein 1, PfEMP1

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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: 7.5
GridMaterial: GOLD / Mesh: 300
VitrificationCryogen name: ETHANE / Chamber humidity: 95 % / Instrument: FEI VITROBOT MARK IV

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Electron microscopy

MicroscopeTFS GLACIOS
Image recordingFilm or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 50.0 e/Å2
Electron beamAcceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.8 µm

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Image processing

Startup modelType of model: INSILICO MODEL
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.1 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 130000
Initial angle assignmentType: ANGULAR RECONSTITUTION
Final angle assignmentType: ANGULAR RECONSTITUTION

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