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- EMDB-16569: PfRH5-PfCyRPA-PfRIPR complex from Plasmodium falciparum bound to ... -
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Open data
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Basic information
Entry | ![]() | |||||||||
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Title | PfRH5-PfCyRPA-PfRIPR complex from Plasmodium falciparum bound to antibody Cy.003 | |||||||||
![]() | composite map | |||||||||
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![]() | Plasmodium falciparum / erythrocyte-invasion / PfRCR / blood stage malaria vaccine / CELL ADHESION | |||||||||
Function / homology | ![]() rhoptry lumen / rhoptry / microneme lumen / microneme / symbiont entry into host / host cell membrane / bicellular tight junction / apical part of cell / heparin binding / cytoplasmic vesicle ...rhoptry lumen / rhoptry / microneme lumen / microneme / symbiont entry into host / host cell membrane / bicellular tight junction / apical part of cell / heparin binding / cytoplasmic vesicle / host extracellular space / host cell surface receptor binding / host cell plasma membrane / protein-containing complex / extracellular region / membrane / plasma membrane Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.0 Å | |||||||||
![]() | Farrell B / Higgins MK | |||||||||
Funding support | ![]()
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![]() | ![]() Title: The PfRCR complex bridges malaria parasite and erythrocyte during invasion. Authors: Brendan Farrell / Nawsad Alam / Melissa N Hart / Abhishek Jamwal / Robert J Ragotte / Hannah Walters-Morgan / Simon J Draper / Ellen Knuepfer / Matthew K Higgins / ![]() Abstract: The symptoms of malaria occur during the blood stage of infection, when parasites invade and replicate within human erythrocytes. The PfPCRCR complex, containing PfRH5 (refs. ), PfCyRPA, PfRIPR, ...The symptoms of malaria occur during the blood stage of infection, when parasites invade and replicate within human erythrocytes. The PfPCRCR complex, containing PfRH5 (refs. ), PfCyRPA, PfRIPR, PfCSS and PfPTRAMP, is essential for erythrocyte invasion by the deadliest human malaria parasite, Plasmodium falciparum. Invasion can be prevented by antibodies or nanobodies against each of these conserved proteins, making them the leading blood-stage malaria vaccine candidates. However, little is known about how PfPCRCR functions during invasion. Here we present the structure of the PfRCR complex, containing PfRH5, PfCyRPA and PfRIPR, determined by cryogenic-electron microscopy. We test the hypothesis that PfRH5 opens to insert into the membrane, instead showing that a rigid, disulfide-locked PfRH5 can mediate efficient erythrocyte invasion. We show, through modelling and an erythrocyte-binding assay, that PfCyRPA-binding antibodies neutralize invasion through a steric mechanism. We determine the structure of PfRIPR, showing that it consists of an ordered, multidomain core flexibly linked to an elongated tail. We also show that the elongated tail of PfRIPR, which is the target of growth-neutralizing antibodies, binds to the PfCSS-PfPTRAMP complex on the parasite membrane. A modular PfRIPR is therefore linked to the merozoite membrane through an elongated tail, and its structured core presents PfCyRPA and PfRH5 to interact with erythrocyte receptors. This provides fresh insight into the molecular mechanism of erythrocyte invasion and opens the way to new approaches in rational vaccine design. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 130.8 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 19.2 KB 19.2 KB | Display Display | ![]() |
Images | ![]() | 68.7 KB | ||
Filedesc metadata | ![]() | 7.1 KB | ||
Others | ![]() | 204 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8cddMC ![]() 8cdeC C: citing same article ( M: atomic model generated by this map |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
File | ![]() | ||||||||||||||||||||
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Annotation | composite map | ||||||||||||||||||||
Voxel size | X=Y=Z: 0.832 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Additional map: composite map after DeepEMhancer
File | emd_16569_additional_1.map | ||||||||||||
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Annotation | composite map after DeepEMhancer | ||||||||||||
Projections & Slices |
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Density Histograms |
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Sample components
-Entire : PfRH5-PfCyRPA-PfRIPR complex bound to Fab fragment from antibody ...
Entire | Name: PfRH5-PfCyRPA-PfRIPR complex bound to Fab fragment from antibody Cy.003 |
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Components |
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-Supramolecule #1: PfRH5-PfCyRPA-PfRIPR complex bound to Fab fragment from antibody ...
Supramolecule | Name: PfRH5-PfCyRPA-PfRIPR complex bound to Fab fragment from antibody Cy.003 type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: ![]() ![]() |
-Macromolecule #1: Rh5-interacting protein
Macromolecule | Name: Rh5-interacting protein / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 124.275094 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: DLIEGIFYEK NEIDKLTFSL DHRVRDNLKT DLILNNNGEN DYAYLNKYVY TILNRDSTEK IKTFFSHNKD MKSCDYFISK EYQSSDKTN QICYKKTFCG VVIPNSEEIK TNKITNDKLY CAHFQSTHII IYYISQPLLL EPHVVYEETF FEKGKNDQIN C QGMYISLR ...String: DLIEGIFYEK NEIDKLTFSL DHRVRDNLKT DLILNNNGEN DYAYLNKYVY TILNRDSTEK IKTFFSHNKD MKSCDYFISK EYQSSDKTN QICYKKTFCG VVIPNSEEIK TNKITNDKLY CAHFQSTHII IYYISQPLLL EPHVVYEETF FEKGKNDQIN C QGMYISLR SVHVHTHNAI LQQETLTYIK NLCDGKNNCK FDFDSIKYEQ KSLTHYLFFI NIQYQCISPL NLQENEMCDV YN DDTHKAT CKYGFNKIEL LKNVCEENYR CTQDICSVNQ FCDGENETCT CKTSLLPSAK NNCEYNDLCT VLNCPEQSTC EQI GNGKKA ECKCENGKYY HNNKCYTKND LELAIKIEPH KKEKFYKNNL YQGKALKPEY IFMQCENGFS IEVINAYVSC YRVS FNLNK LKYVTESLKK MCDGKTKCAY GNTIDPIDDL NHHNICNNFN TIFKYDYLCV FNNQQITSDK NSHLHSNIPS LYQSS ILPD IQKSKFHLIS RNSRTNQYPH NQISMLEIQN EISSHNSNQF STDPHTNSNN INNMNIKKVE IFRSRFSSKL QCQGGK INI DKAILKGGEG CNDLLLTNSL KSYCNDLSEC DIGLIYHFDT YCINDQYLFV SYSCSNLCNK CHQQSTCYGN RFNYDCF CD NPYISKYGNK LCERPNDCES VLCSQNQVCQ ILPNDKLICQ CEEGYKNVKG KCVPDNKCDL SCPSNKVCVI ENGKQTCK C SERFVLENGV CICANDYKME DGINCIAKNK CKRKEYENIC TNPNEMCAYN EETDIVKCEC KEHYYRSSRG ECILNDYCK DINCKENEEC SIVNFKPECV CKENLKKNNK GECIYENSCL INEGNCPKDS KCIYREYKPH ECVCNKQGHV AVNGKCVLED KCVHNKKCS ENSICVNVMN KEPICVCTYN YYKKDGVCLI QNPCLKDNGG CSRNSECTFK YSKIQCTCKE NYKNKDDSCV P NTNEYDES FTFQYNDDAS IILGACGMIE FSYIYNQIIW KIQNSKESYV FYYDYPTAGN IEVQIKNEIF HTIIYLKKKI GN SVIYDDF QVDHQTCIYE NVFYYSNQNE PEA UniProtKB: Rh5-interacting protein |
-Macromolecule #2: Cysteine-rich protective antigen
Macromolecule | Name: Cysteine-rich protective antigen / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 40.184039 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: DSRHVFIRTE LSFIKNNVPC IRDMFFIYKR ELYNICLDDL KGEEDETHIY VQKKVKDSWI TLNDLFKETD LTGRPHIFAY VDVEEIIIL LCEDEEFSNR KKDMTCHRFY SNDGKEYNNA EITISDYILK DKLLSSYVSL PLKIENREYF LICGVSPYKF K DDNKKDDI ...String: DSRHVFIRTE LSFIKNNVPC IRDMFFIYKR ELYNICLDDL KGEEDETHIY VQKKVKDSWI TLNDLFKETD LTGRPHIFAY VDVEEIIIL LCEDEEFSNR KKDMTCHRFY SNDGKEYNNA EITISDYILK DKLLSSYVSL PLKIENREYF LICGVSPYKF K DDNKKDDI LCMASHDKGE TWGTKIVIKY DNYKLGVQYF FLRPYISKND LSFHFYVGDN INNVKNVNFI ECTHEKDLEF VC SNRDFLK DNKVLQDVST LNDEYIVSYG NDNNFAECYI FFNNENSILI KPEKYGNTAA GCYGGTFVKI DENRALFIYS SSQ GIYNIH TIYYANYEGG GGSEPEA UniProtKB: Cysteine-rich protective antigen |
-Macromolecule #3: Reticulocyte-binding protein homolog 5
Macromolecule | Name: Reticulocyte-binding protein homolog 5 / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 60.157004 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: FENAIKKTKN QENNLTLLPI KSTEEEKDDI KNGKDIKKEI DNDKENIKTN NAKDHSTYIK SYLNTNVNDG LKYLFIPSHN SFIKKYSVF NQINDGMLLN EKNDVKNNED YKNVDYKNVN FLQYHFKELS NYNIANSIDI LQEKEGHLDF VIIPHYTFLD Y YKHLSYNS ...String: FENAIKKTKN QENNLTLLPI KSTEEEKDDI KNGKDIKKEI DNDKENIKTN NAKDHSTYIK SYLNTNVNDG LKYLFIPSHN SFIKKYSVF NQINDGMLLN EKNDVKNNED YKNVDYKNVN FLQYHFKELS NYNIANSIDI LQEKEGHLDF VIIPHYTFLD Y YKHLSYNS IYHKSSTYGK YIAVDAFIKK INEAYDKVKS KCNDIKNDLI ATIKKLEHPY DINNKNDDSY RYDISEEIDD KS EETDDET EEVEDSIQDT DSNHTPSNKK KNDLMNRAFK KMMDEYNTKK KKLIKCIKNH ENDFNKICMD MKNYGTNLFE QLS CYNNNF CNTNGIRYHY DEYIHKLILS VKSKNLNKDL SDMTNILQQS ELLLTNLNKK MGSYIYIDTI KFIHKEMKHI FNRI EYHTK IINDKTKIIQ DKIKLNIWRT FQKDELLKRI LDMSNEYSLF ITSDHLRQML YNTFYSKEKH LNNIFHHLIY VLQMK FNDV PIKMEYFQTY KKNKPLTQ UniProtKB: Reticulocyte-binding protein homolog 5 |
-Macromolecule #4: Cy.003 light chain
Macromolecule | Name: Cy.003 light chain / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 22.083281 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: ALTQPSSVSA NPGETVKITC SGGSSSYYGW YQQKSPGSAP VTLIYNNQKR PSDIPSRFSG SKSGSTGTLT ITGVQAEDEA VYFCGSRDN SGGIFGAGTT LTVLRTVAAP SVFIFPPSDE QLKSGTASVV CLLNNFYPRE AKVQWKVDNA LQSGNSQESV T EQDSKDST ...String: ALTQPSSVSA NPGETVKITC SGGSSSYYGW YQQKSPGSAP VTLIYNNQKR PSDIPSRFSG SKSGSTGTLT ITGVQAEDEA VYFCGSRDN SGGIFGAGTT LTVLRTVAAP SVFIFPPSDE QLKSGTASVV CLLNNFYPRE AKVQWKVDNA LQSGNSQESV T EQDSKDST YSLSSTLTLS KADYEKHKVY ACEVTHQGLS SPVTKSFNR |
-Macromolecule #5: Cy.003 heavy chain
Macromolecule | Name: Cy.003 heavy chain / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 23.362984 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: AVTLDESGGG LQTPGGALSL VCKGSGFFSF SSYTMQWVRQ APGKGLEWVA SISSGGGTNY GAAVKGRATI SRDNGQSTLR LQLNNLRAE DTGTYYCAKH GVNGCDWSYS VGCVDAWGHG TEVIVSSAST KGPSVFPLAP SSKSTSGGTA ALGCLVKDYF P EPVTVSWN ...String: AVTLDESGGG LQTPGGALSL VCKGSGFFSF SSYTMQWVRQ APGKGLEWVA SISSGGGTNY GAAVKGRATI SRDNGQSTLR LQLNNLRAE DTGTYYCAKH GVNGCDWSYS VGCVDAWGHG TEVIVSSAST KGPSVFPLAP SSKSTSGGTA ALGCLVKDYF P EPVTVSWN SGALTSGVHT FPAVLQSSGL YSLSSVVTVP SSSLGTQTYI CNVNHKPSNT KVDKKVEP |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 48.97 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 3.0 µm / Nominal defocus min: 1.0 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Startup model | Type of model: NONE |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.0 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 500277 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |