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- EMDB-41821: Plasmodium falciparum gametocyte surface protein Pfs48/45 in comp... -

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Basic information

Entry
Database: EMDB / ID: EMD-41821
TitlePlasmodium falciparum gametocyte surface protein Pfs48/45 in complex with neutralizing antibodies
Map datacryoEM map of Pfs48/45-TB31F-RUPA44-RUPA58-RUPA154 complex
Sample
  • Complex: complex of Pfs48/45-TB31F-RUPA44-RUPA58-RUPA154
    • Protein or peptide: Pfs48/45- scTB31F
    • Protein or peptide: RUPA154 Fab Heavy Chain
    • Protein or peptide: RUPA154 Fab Light Chain
    • Protein or peptide: RUPA58 Fab Heavy Chain
    • Protein or peptide: RUPA58 Fab Light Chain
    • Protein or peptide: RUPA44 Fab Heavy Chain
    • Protein or peptide: RUPA44 Fab Light Chain
Keywordstransmission blocking vaccine / antibody / malaria / cryoEM / CELL INVASION
Biological speciesPlasmodium falciparum 3D7 (eukaryote) / Plasmodium falciparum (malaria parasite P. falciparum) / Homo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.9 Å
AuthorsKucharska I / Hailemariam S / Ivanochko D / Rubinstein J / Julien JP
Funding support Canada, Netherlands, 8 items
OrganizationGrant numberCountry
Canadian Institutes of Health Research (CIHR) Canada
CIFAR Azrieli Global Scholars Canada
Ontario Early Researcher Awards Canada
Canada Research Chairs Canada
Netherlands Organisation for Scientific Research (NWO)192.061 Netherlands
Other governmentCanada Graduate Scholarships Doctoral Award
Canada Foundation for Innovation Canada
Ontario Research Fund Canada
CitationJournal: Nat Struct Mol Biol / Year: 2025
Title: Structural elucidation of full-length Pfs48/45 in complex with potent monoclonal antibodies isolated from a naturally exposed individual.
Authors: Iga Kucharska / Danton Ivanochko / Sophia Hailemariam / Maartje R Inklaar / Hee Ryung Kim / Karina Teelen / Rianne Stoter / Marga van de Vegte-Bolmer / Geert-Jan van Gemert / Anthony Semesi ...Authors: Iga Kucharska / Danton Ivanochko / Sophia Hailemariam / Maartje R Inklaar / Hee Ryung Kim / Karina Teelen / Rianne Stoter / Marga van de Vegte-Bolmer / Geert-Jan van Gemert / Anthony Semesi / Brandon McLeod / Ahyoung Ki / Won-Kyu Lee / John L Rubinstein / Matthijs M Jore / Jean-Philippe Julien /
Abstract: Biomedical interventions that block the transmission of Plasmodium falciparum (Pf) from humans to mosquitoes may be critical for malaria elimination. Pfs48/45, a gamete-surface protein essential for ...Biomedical interventions that block the transmission of Plasmodium falciparum (Pf) from humans to mosquitoes may be critical for malaria elimination. Pfs48/45, a gamete-surface protein essential for Pf development in the mosquito midgut, is a target of clinical-stage transmission-blocking vaccines and monoclonal antibodies (mAbs) that disrupt Pf transmission to mosquitoes. Antibodies directed to domain 3 of Pfs48/45 have been structurally and functionally described; however, in-depth information about other inhibitory epitopes on Pfs48/45 is currently limited. Here, we present a cryo-electron microscopy structure of full-length Pfs48/45 in complex with potent human mAbs targeting all three domains. Our data indicate that although Pfs48/45 domains 1 and 2 are rigidly coupled, there is substantial conformational flexibility between domains 2 and 3. Characterization of mAbs against domain 1 revealed the presence of a conformational epitope class that is largely conserved across Pf field isolates and is associated with recognition by potent antibodies. Our study provides insights into epitopes across full-length Pfs48/45 and has implications for the design of next-generation malaria interventions.
History
DepositionSep 1, 2023-
Header (metadata) releaseMar 12, 2025-
Map releaseMar 12, 2025-
UpdateAug 27, 2025-
Current statusAug 27, 2025Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_41821.png

Downloads & links

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Map

FileDownload / File: emd_41821.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationcryoEM map of Pfs48/45-TB31F-RUPA44-RUPA58-RUPA154 complex
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.03 Å/pix.
x 320 pix.
= 329.6 Å		1.03 Å/pix.
x 320 pix.
= 329.6 Å		1.03 Å/pix.
x 320 pix.
= 329.6 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.03 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 1.5
Minimum - Maximum-0.26868752 - 20.423639999999999
Average (Standard dev.)0.027814917 (±0.4553505)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions320320320
Spacing320320320
CellA=B=C: 329.59998 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: half map of Pfs48/45-TB31F-RUPA44-RUPA58-RUPA154 complex

Fileemd_41821_half_map_1.map
Annotationhalf map of Pfs48/45-TB31F-RUPA44-RUPA58-RUPA154 complex
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: half map of Pfs48/45-TB31F-RUPA44-RUPA58-RUPA154 complex

Fileemd_41821_half_map_2.map
Annotationhalf map of Pfs48/45-TB31F-RUPA44-RUPA58-RUPA154 complex
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 Pfs48/45-TB31F-RUPA44-RUPA58-RUPA154

EntireName: complex of Pfs48/45-TB31F-RUPA44-RUPA58-RUPA154
Components
  • Complex: complex of Pfs48/45-TB31F-RUPA44-RUPA58-RUPA154
    • Protein or peptide: Pfs48/45- scTB31F
    • Protein or peptide: RUPA154 Fab Heavy Chain
    • Protein or peptide: RUPA154 Fab Light Chain
    • Protein or peptide: RUPA58 Fab Heavy Chain
    • Protein or peptide: RUPA58 Fab Light Chain
    • Protein or peptide: RUPA44 Fab Heavy Chain
    • Protein or peptide: RUPA44 Fab Light Chain

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Supramolecule #1: complex of Pfs48/45-TB31F-RUPA44-RUPA58-RUPA154

SupramoleculeName: complex of Pfs48/45-TB31F-RUPA44-RUPA58-RUPA154 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Plasmodium falciparum 3D7 (eukaryote)

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Macromolecule #1: Pfs48/45- scTB31F

MacromoleculeName: Pfs48/45- scTB31F / type: protein_or_peptide / ID: 1 / Enantiomer: LEVO
Source (natural)Organism: Plasmodium falciparum (malaria parasite P. falciparum)
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: NNDFCKPSSL NSEISGFIGY KCNFSNEGVH NLKPDMRERR SIFCTIHSYF IYDKIRLIIP KKSSSPEFKI LPEKCFQKVY TDYENRVET DISELGLIEY EIEENDTNPN YNERTITISP FSPKDIEFFC FCDNTEKVIS SIEGRSAMVH VRVLKYPHNI L FTNLTNDL ...String:
NNDFCKPSSL NSEISGFIGY KCNFSNEGVH NLKPDMRERR SIFCTIHSYF IYDKIRLIIP KKSSSPEFKI LPEKCFQKVY TDYENRVET DISELGLIEY EIEENDTNPN YNERTITISP FSPKDIEFFC FCDNTEKVIS SIEGRSAMVH VRVLKYPHNI L FTNLTNDL FTYLPKTYNE SNFVSNVLEV ELNDGELFVL ACELINKKCF QEGKEKALYK SNKIIYHKNL TIFKAPFYVT SK DVNTECT CKFKNNNYKI VLKPKYEKKV IHGCNFSSNV SSKYTFTDSL DISLVDDSAH ISCNVHLSEP KYNHLVGLNC PGD IIPDCF FQVYQPEREE LEPSNIVYLS SQINIGDIEY YEDAEGDDKI KLFLIVGSVP KTTSFTCICK KDKKSAYMTV TIDS AGGSG GSGGSGGSGG SGGSGGSEVQ LVQSGGGLVQ PGGSLRLSCA ASGFTFNNYW MSWVRQAPGK GLEWVSSISN IGGTI YYPD SVKGRFTISR DNSKNTLYLQ MNSLRAEDTA VYYCTRDLRM SDYFDYWGQG TMVTVSSAST KGPSVFPLAP SSKSTS GGT AALGCLVKDY FPEPVTVSWN SGALTSGVHT FPAVLQSSGL YSLSSVVTVP SSSLGTQTYI CNVNHKPSNT KVDKKVE PK SCGGGGSGGG GSGGGGSGGG GSGGGGSGGG GSGGGGSGGG GSGGGGSGGG GSGGGGSGGG GSGGGGSGGG GSNFMLTQ P HSVSESPGKT VTISCTRSTG NIGSNYVSWY QQRPGSSPTT VIYRDDQRPS GVPDRFSGSI DRSSNSASLT ISGLKTEDE ADYYCHSYST GMYIFGGGTK LTVLGQPKAA PSVTLFPPSS EELQANKATL VCLISDFYPG AVTVAWKADS SPVKAGVETT TPSKQSNNK YAASSYLSLT PEQWKSHRSY SCQVTHEGST VEKTVAPTEC SGTKHHHHHH

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Macromolecule #3: RUPA154 Fab Heavy Chain

MacromoleculeName: RUPA154 Fab Heavy Chain / type: protein_or_peptide / ID: 3 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: QVQLVQSGAE VRKPGASVKV SCRTSGYTFT DYYMHWVRQA PGEGLEWMGS INPKSGGTSY AERFQGRVTM TMETSVSTAY LDLSSLRSD DTAVYYCARL LYSRAVYYYG MDVWGQGTTV TVSSASTKGP SVFPLAPSSK STSGGTAALG CLVKDYFPEP V TVSWNSGA ...String:
QVQLVQSGAE VRKPGASVKV SCRTSGYTFT DYYMHWVRQA PGEGLEWMGS INPKSGGTSY AERFQGRVTM TMETSVSTAY LDLSSLRSD DTAVYYCARL LYSRAVYYYG MDVWGQGTTV TVSSASTKGP SVFPLAPSSK STSGGTAALG CLVKDYFPEP V TVSWNSGA LTSGVHTFPA VLQSSGLYSL SSVVTVPSSS LGTQTYICNV NHKPSNTKVD KKVEPKSC

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Macromolecule #4: RUPA154 Fab Light Chain

MacromoleculeName: RUPA154 Fab Light Chain / type: protein_or_peptide / ID: 4 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: IQMTQSPSSL SASVGDRVTI TCRASQIIST YLNWYQHKPG KAPKLLIKSA STLQSGVPSR FSGSGSGTDF TLTITSLQPE DFATFYCQQ SYRDPITFGQ GTRLEIKRTV AAPSVFIFPP SDEQLKSGTA SVVCLLNNFY PREAKVQWKV DNALQSGNSQ E SVTEQDSK ...String:
IQMTQSPSSL SASVGDRVTI TCRASQIIST YLNWYQHKPG KAPKLLIKSA STLQSGVPSR FSGSGSGTDF TLTITSLQPE DFATFYCQQ SYRDPITFGQ GTRLEIKRTV AAPSVFIFPP SDEQLKSGTA SVVCLLNNFY PREAKVQWKV DNALQSGNSQ E SVTEQDSK DSTYSLSSTL TLSKADYEKH KVYACEVTHQ GLSSPVTKSF NRGEC

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Macromolecule #5: RUPA58 Fab Heavy Chain

MacromoleculeName: RUPA58 Fab Heavy Chain / type: protein_or_peptide / ID: 5 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: QVQLVQSGPE AKKPGASVKV SCQASGYPFS GYYMHWLRQA PGQGLEWMGW MNPNSGGTKY AQRFQGRVTM TRDTSISTAH MELRGLRSDD TAVYYCARDY CTGSSCYRTD YDYWGQGTLV TVSSASTKGP SVFPLAPSSK STSGGTAALG CLVKDYFPEP VTVSWNSGAL ...String:
QVQLVQSGPE AKKPGASVKV SCQASGYPFS GYYMHWLRQA PGQGLEWMGW MNPNSGGTKY AQRFQGRVTM TRDTSISTAH MELRGLRSDD TAVYYCARDY CTGSSCYRTD YDYWGQGTLV TVSSASTKGP SVFPLAPSSK STSGGTAALG CLVKDYFPEP VTVSWNSGAL TSGVHTFPAV LQSSGLYSLS SVVTVPSSSL GTQTYICNVN HKPSNTKVDK KVEPKSC

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Macromolecule #6: RUPA58 Fab Light Chain

MacromoleculeName: RUPA58 Fab Light Chain / type: protein_or_peptide / ID: 6 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: IQMTQSPSSL SASVGDRVTI TCRASQIIST YLNWYQHKPG KAPKLLIKSA STLQSGVPSR FSGSGSGTDF TLTITSLQPE DFATFYCQQ SYRDPITFGQ GTRLEIKRTV AAPSVFIFPP SDEQLKSGTA SVVCLLNNFY PREAKVQWKV DNALQSGNSQ E SVTEQDSK ...String:
IQMTQSPSSL SASVGDRVTI TCRASQIIST YLNWYQHKPG KAPKLLIKSA STLQSGVPSR FSGSGSGTDF TLTITSLQPE DFATFYCQQ SYRDPITFGQ GTRLEIKRTV AAPSVFIFPP SDEQLKSGTA SVVCLLNNFY PREAKVQWKV DNALQSGNSQ E SVTEQDSK DSTYSLSSTL TLSKADYEKH KVYACEVTHQ GLSSPVTKSF NRGEC

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Macromolecule #7: RUPA44 Fab Heavy Chain

MacromoleculeName: RUPA44 Fab Heavy Chain / type: protein_or_peptide / ID: 7 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: QLQLQESGPG LVKPSETLSL TCTVSGGSIS RSPYYWGWIR QPPGKGLEWF GSIYNNGSTY YNPPLKSRLT ISVDTSKNQF SLKLSSVTAA DTAVYYCARH GGSTGMKVVV IAPPDYWGQG TLVTVSS AS TKGPSVFPLA PSSKSTSGGT AALGCLVKDY FPEPVTVSWN ...String:
QLQLQESGPG LVKPSETLSL TCTVSGGSIS RSPYYWGWIR QPPGKGLEWF GSIYNNGSTY YNPPLKSRLT ISVDTSKNQF SLKLSSVTAA DTAVYYCARH GGSTGMKVVV IAPPDYWGQG TLVTVSS AS TKGPSVFPLA PSSKSTSGGT AALGCLVKDY FPEPVTVSWN SGALTSGVHT FPAVLQSSGL YSLSSVVTVP SSSLGTQTYI CNVNHKPSNT KVDKKVEPKS C

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Macromolecule #8: RUPA44 Fab Light Chain

MacromoleculeName: RUPA44 Fab Light Chain / type: protein_or_peptide / ID: 8 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: DIQMTQSPAT LSASVGDRVT ITCRASQSIS SWLAWYQQKP GEAPKLLIYK ASSLQSGVPS RFSGSGSGTK FSLTISSLQP DDFATFYCQQ YHSYPYTFGQ GTKLEIK RT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF YPREAKVQWK VDNALQSGNS QESVTEQDSK ...String:
DIQMTQSPAT LSASVGDRVT ITCRASQSIS SWLAWYQQKP GEAPKLLIYK ASSLQSGVPS RFSGSGSGTK FSLTISSLQP DDFATFYCQQ YHSYPYTFGQ GTKLEIK RT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF YPREAKVQWK VDNALQSGNS QESVTEQDSK DSTYSLSSTL TLSKADYEKH KVYACEVTHQ GLSSPVTKSF NRGEC

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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

Concentration0.5 mg/mL
BufferpH: 7
Component:
ConcentrationFormulaName
50.0 mM2-Amino-2-(hydroxymethyl)propane-1,3-diolTris-buffered saline
150.0 mMNaClSodium chloride
GridModel: Homemade / Material: GOLD / Mesh: 400 / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 15 sec. / Pretreatment - Atmosphere: AIR
VitrificationCryogen name: ETHANE / Chamber humidity: 90 % / Chamber temperature: 277 K / Instrument: LEICA EM GP
Details: sample was frozen with Leica Automatic Plunge Freezer EM GP2.

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: FEI FALCON IV (4k x 4k) / Number real images: 7744 / Average exposure time: 8.83 sec. / Average electron dose: 48.69 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.5 µm / Nominal magnification: 75000
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

Particle selectionNumber selected: 2824624
CTF correctionSoftware - Name: cryoSPARC (ver. 4) / Type: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: NONE
Final reconstructionApplied symmetry - Point group: C1 (asymmetric) / Algorithm: FOURIER SPACE / Resolution.type: BY AUTHOR / Resolution: 3.9 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC (ver. 4) / Number images used: 306744
Initial angle assignmentType: NOT APPLICABLE
Final angle assignmentType: NOT APPLICABLE

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