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- EMDB-22325: Cryo-EM structure of P. falciparum VAR2CSA FCR3 domains DBL5 and ... -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-22325 | |||||||||
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Title | Cryo-EM structure of P. falciparum VAR2CSA FCR3 domains DBL5 and DBL6 at 4.69 A | |||||||||
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Function / homology | ![]() | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.69 Å | |||||||||
![]() | Ma R / Tolia NH | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural basis for placental malaria mediated by Plasmodium falciparum VAR2CSA. Authors: Rui Ma / Tengfei Lian / Rick Huang / Jonathan P Renn / Jennifer D Petersen / Joshua Zimmerberg / Patrick E Duffy / Niraj H Tolia / ![]() Abstract: Plasmodium falciparum VAR2CSA binds to chondroitin sulfate A (CSA) on the surface of the syncytiotrophoblast during placental malaria. This interaction facilitates placental sequestration of malaria ...Plasmodium falciparum VAR2CSA binds to chondroitin sulfate A (CSA) on the surface of the syncytiotrophoblast during placental malaria. This interaction facilitates placental sequestration of malaria parasites resulting in severe health outcomes for both the mother and her offspring. Furthermore, CSA is presented by diverse cancer cells and specific targeting of cells by VAR2CSA may become a viable approach for cancer treatment. In the present study, we determined the cryo-electron microscopy structures of the full-length ectodomain of VAR2CSA from P. falciparum strain NF54 in complex with CSA, and VAR2CSA from a second P. falciparum strain FCR3. The architecture of VAR2CSA is composed of a stable core flanked by a flexible arm. CSA traverses the core domain by binding within two channels and CSA binding does not induce major conformational changes in VAR2CSA. The CSA-binding elements are conserved across VAR2CSA variants and are flanked by polymorphic segments, suggesting immune selection outside the CSA-binding sites. This work provides paths for developing interventions against placental malaria and cancer. | |||||||||
History |
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Structure visualization
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 58.5 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 12.4 KB 12.4 KB | Display Display | ![]() |
Images | ![]() | 39.3 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7jgfMC ![]() 7jgdC ![]() 7jgeC ![]() 7jggC ![]() 7jghC C: citing same article ( M: atomic model generated by this map |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Map
File | ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Voxel size | X=Y=Z: 1.058 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
-Entire : VAR2CSA FCR3
Entire | Name: VAR2CSA FCR3 |
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Components |
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-Supramolecule #1: VAR2CSA FCR3
Supramolecule | Name: VAR2CSA FCR3 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: ![]() ![]() |
Recombinant expression | Organism: ![]() |
-Macromolecule #1: Erythrocyte membrane protein 1
Macromolecule | Name: Erythrocyte membrane protein 1 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 308.823188 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: TGMDSTSTIA NKIEEYLGAK SDDSKIDELL KADPSEVEYY RSGGDGDYLK NNICKITVNH SDSGKYDPCE KKLPPYDDND QWKCQQNSS DGSGKPENIC VPPRRERLCT YNLENLKFDK IRDNNAFLAD VLLTARNEGE KIVQNHPDTN SSNVCNALER S FADLADII ...String: TGMDSTSTIA NKIEEYLGAK SDDSKIDELL KADPSEVEYY RSGGDGDYLK NNICKITVNH SDSGKYDPCE KKLPPYDDND QWKCQQNSS DGSGKPENIC VPPRRERLCT YNLENLKFDK IRDNNAFLAD VLLTARNEGE KIVQNHPDTN SSNVCNALER S FADLADII RGTDQWKGTN SNLEKNLKQM FAKIRENDKV LQDKYPKDQK YTKLREAWWN ANRQKVWEVI TCGARSNDLL IK RGWRTSG KSDRKKNFEL CRKCGHYEKE VPTKLDYVPQ FLRWLTEWIE DFYREKQNLI DDMERHREEC TREDHKSKEG TSY CSTCKD KCKKYCECVK KWKTEWENQE NKYKDLYEQN KNKTSQKNTS RYDDYVKDFF EKLEANYSSL ENYIKGDPYF AEYA TKLSF ILNPSDANNP SGETANHNDE ACNCNESGIS SVGQAQTSGP SSNKTCITHS SIKTNKKKEC KDVKLGVREN DKDLK ICVI EDTSLSGVDN CCCQDLLGIL QENCSDNKRG SSSNDSCDNK NQDECQKKLE KVFASLTNGY KCDKCKSGTS RSKKKW IWK KSSGNEEGLQ EEYANTIGLP PRTQSLYLGN LPKLENVCED VKDINFDTKE KFLAGCLIVS FHEGKNLKKR YPQNKNS GN KENLCKALEY SFADYGDLIK GTSIWDNEYT KDLELNLQNN FGKLFGKYIK KNNTAEQDTS YSSLDELRES WWNTNKKY I WTAMKHGAEM NITTCNADGS VTGSGSSCDD IPTIDLIPQY LRFLQEWVEN FCEQRQAKVK DVITNCKSCK ESGNKCKTE CKTKCKDECE KYKKFIEACG TAGGGIGTAG SPWSKRWDQI YKRYSKHIED AKRNRKAGTK NCGTSSTTNA AASTDENKCV QSDIDSFFK HLIDIGLTTP SSYLSNVLDD NICGADKAPW TTYTTYTTTE KCNKERDKSK SQSSDTLVVV NVPSPLGNTP Y RYKYACQC KIPTNEETCD DRKEYMNQWS CGSARTMKRG YKNDNYELCK YNGVDVKPTT VRSNSSKLDG NDVTFFNLFE QW NKEIQYQ IEQYMTNANI SCIDEKEVLD SVSDEGTPKV RGGYEDGRNN NTDQGTNCKE KCKCYKLWIE KINDQWGKQK DNY NKFRSK QIYDANKGSQ NKKVVSLSNF LFFSCWEEYI QKYFNGDWSK IKNIGSDTFE FLIKKCGNNS AHGEEIFNEK LKNA EKKCK ENESTDTNIN KSETSCDLNA TNYIRGCQSK TYDGKIFPGK GGEKQWICKD TIIHGDTNGA CIPPRTQNLC VGELW DKSY GGRSNIKNDT KELLKEKIKN AIHKETELLY EYHDTGTAII SKNDKKGQKG KNDPNGLPKG FCHAVQRSFI DYKNMI LGT SVNIYEHIGK LQEDIKKIIE KGTPQQKDKI GGVGSSTENV NAWWKGIERE MWDAVRCAIT KINKKNNNSI FNGDECG VS PPTGNDEDQS VSWFKEWGEQ FCIERLRYEQ NIREACTING KNEKKCINSK SGQGDKIQGA CKRKCEKYKK YISEKKQE W DKQKTKYENK YVGKSASDLL KENYPECISA NFDFIFNDNI EYKTYYPYGD YSSICSCEQV KYYKYNNAEK KNNKSLCYE KDNDMTWSKK YIKKLENGRS LEGVYVPPRR QQLCLYELFP IIIKNEEGME KAKEELLETL QIVAEREAYY LWKQYNPTGK GIDDANKKA CCAIRGSFYD LEDIIKGNDL VHDEYTKYID SKLNEIFGSS DTNDIDTKRA RTDWWENETI TNGTDRKTIR Q LVWDAMQS GVRYAVEEKN ENFPLCMGVE HIGIAKPQFI RWLEEWTNEF CEKYTKYFED MKSKCDPPKR ADTCGDNSNI EC KKACANY TNWLNPKRIE WNGMSNYYNK IYRKSNKESE GGKDYSMIMA PTVIDYLNKR CHGEINGNYI CCSCKNIGAY NTT SGTVNK KLQKKETECE EEKGPLDLMN EVLNKMDKKY SAHKMKCTEV YLEHVEEQLN EIDNAIKDYK LYPLDRCFDD QTKM KVCDL IADAIGCKDK TKLDELDEWN DMDLRGTYNK HKGVLIPPRR RQLCFSRIVR GPANLRSLNE FKEEILKGAQ SEGKF LGNY YKEHKDKEKA LEAMKNSFYD YEDIIKGTDM LTNIEFKDIK IKLDRLLEKE TNNTKKAEDW WKTNKKSIWN AMLCGY KKS GNKIIDPSWC TIPTTETPPQ FLRWIKEWGT NVCIQKQEHK EYVKSKCSNV TNLGAQASES NNCTSEIKKY QEWSRKR SI RWETISKRYK KYKRMDILKD VKEPDANTYL REHCSKCPCG FNDMEEMNNN EDNEKEAFKQ IKEQVKIPAE LEDVIYRI K HHEYDKGNDY ICNKYKNIHD RMKKNNGNFV TDNFVKKSWE ISNGVLIPPR RKNLFLYIDP SKICEYKKDP KLFKDFIYW SAFTEVERLK KAYGGARAKV VHAMKYSFTD IGSIIKGDDM MEKNSSDKIG KILGDTDGQN EKRKKWWDMN KYHIWESMLC GYREAEGDT ETNENCRFPD IESVPQFLRW FQEWSENFCD RRQKLYDKLN SECISAECTN GSVDNSKCTH ACVNYKNYIL T KKTEYEIQ TNKYDNEFKN KNSNDKDAPD YLKEKCNDNK CECLNKHIDD KNKTWKNPYE TLEDTFKSKC DCPKPLPSPI KP DDLPPQA DEPFGTKHHH HHH |
-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: 7.4 |
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Grid | Details: unspecified |
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 K2 SUMMIT (4k x 4k) / Average electron dose: 71.2 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 4.69 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 271442 |
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Initial angle assignment | Type: PROJECTION MATCHING |
Final angle assignment | Type: ANGULAR RECONSTITUTION |