[English] 日本語

- EMDB-41821: Plasmodium falciparum gametocyte surface protein Pfs48/45 in comp... -
+
Open data
-
Basic information
Entry | ![]() | |||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Title | Plasmodium falciparum gametocyte surface protein Pfs48/45 in complex with neutralizing antibodies | |||||||||||||||||||||||||||
![]() | cryoEM map of Pfs48/45-TB31F-RUPA44-RUPA58-RUPA154 complex | |||||||||||||||||||||||||||
![]() |
| |||||||||||||||||||||||||||
![]() | transmission blocking vaccine / antibody / malaria / cryoEM / CELL INVASION | |||||||||||||||||||||||||||
Biological species | ![]() ![]() ![]() ![]() ![]() | |||||||||||||||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.9 Å | |||||||||||||||||||||||||||
![]() | Kucharska I / Hailemariam S / Ivanochko D / Rubinstein J / Julien JP | |||||||||||||||||||||||||||
Funding support | ![]() ![]()
| |||||||||||||||||||||||||||
![]() | ![]() 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 |
|
-
Structure visualization
Supplemental images |
---|
-
Downloads & links
-EMDB archive
Map data | ![]() | 25.2 MB | ![]() | |
---|---|---|---|---|
Header (meta data) | ![]() ![]() | 25.5 KB 25.5 KB | Display Display | ![]() |
Images | ![]() | 470.1 KB | ||
Filedesc metadata | ![]() | 6.7 KB | ||
Others | ![]() ![]() | 4.3 MB 4.3 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
-
Links
EMDB pages | ![]() ![]() |
---|
-
Map
File | ![]() | ||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | cryoEM map of Pfs48/45-TB31F-RUPA44-RUPA58-RUPA154 complex | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.03 Å | ||||||||||||||||||||||||||||||||||||
Density |
| ||||||||||||||||||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
|
-Supplemental data
-Half map: half map of Pfs48/45-TB31F-RUPA44-RUPA58-RUPA154 complex
File | emd_41821_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | half map of Pfs48/45-TB31F-RUPA44-RUPA58-RUPA154 complex | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: half map of Pfs48/45-TB31F-RUPA44-RUPA58-RUPA154 complex
File | emd_41821_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | half map of Pfs48/45-TB31F-RUPA44-RUPA58-RUPA154 complex | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-
Sample components
-Entire : complex of Pfs48/45-TB31F-RUPA44-RUPA58-RUPA154
Entire | Name: complex of Pfs48/45-TB31F-RUPA44-RUPA58-RUPA154 |
---|---|
Components |
|
-Supramolecule #1: complex of Pfs48/45-TB31F-RUPA44-RUPA58-RUPA154
Supramolecule | Name: complex of Pfs48/45-TB31F-RUPA44-RUPA58-RUPA154 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
---|---|
Source (natural) | Organism: ![]() ![]() |
-Macromolecule #1: Pfs48/45- scTB31F
Macromolecule | Name: Pfs48/45- scTB31F / type: protein_or_peptide / ID: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: ![]() ![]() |
Recombinant expression | Organism: ![]() |
Sequence | String: 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 |
-Macromolecule #3: RUPA154 Fab Heavy Chain
Macromolecule | Name: RUPA154 Fab Heavy Chain / type: protein_or_peptide / ID: 3 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: ![]() |
Recombinant expression | Organism: ![]() |
Sequence | String: 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 |
-Macromolecule #4: RUPA154 Fab Light Chain
Macromolecule | Name: RUPA154 Fab Light Chain / type: protein_or_peptide / ID: 4 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: ![]() |
Recombinant expression | Organism: ![]() |
Sequence | String: 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 |
-Macromolecule #5: RUPA58 Fab Heavy Chain
Macromolecule | Name: RUPA58 Fab Heavy Chain / type: protein_or_peptide / ID: 5 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: ![]() |
Recombinant expression | Organism: ![]() |
Sequence | String: 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 |
-Macromolecule #6: RUPA58 Fab Light Chain
Macromolecule | Name: RUPA58 Fab Light Chain / type: protein_or_peptide / ID: 6 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: ![]() |
Recombinant expression | Organism: ![]() |
Sequence | String: 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 |
-Macromolecule #7: RUPA44 Fab Heavy Chain
Macromolecule | Name: RUPA44 Fab Heavy Chain / type: protein_or_peptide / ID: 7 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: ![]() |
Recombinant expression | Organism: ![]() |
Sequence | String: 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 |
-Macromolecule #8: RUPA44 Fab Light Chain
Macromolecule | Name: RUPA44 Fab Light Chain / type: protein_or_peptide / ID: 8 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: ![]() |
Recombinant expression | Organism: ![]() |
Sequence | String: 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 |
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
![]() | single particle reconstruction |
Aggregation state | particle |
-
Sample preparation
Concentration | 0.5 mg/mL | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Buffer | pH: 7 Component:
| |||||||||
Grid | Model: Homemade / Material: GOLD / Mesh: 400 / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 15 sec. / Pretreatment - Atmosphere: AIR | |||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 90 % / Chamber temperature: 277 K / Instrument: LEICA EM GP Details: sample was frozen with Leica Automatic Plunge Freezer EM GP2. |
-
Electron microscopy
Microscope | FEI TITAN KRIOS |
---|---|
Image recording | Film 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 beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination 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 stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |