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- EMDB-12018: VAR2CSA full ectodomain in present of plCS, DBL1-DBL4 -

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Open data


ID or keywords:

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Basic information

Entry
Database: EMDB / ID: EMD-12018
TitleVAR2CSA full ectodomain in present of plCS, DBL1-DBL4
Map data
Sample
  • Complex: VAR2CSA in presence of plCS, DBl1-DBL4
    • Protein or peptide: VAR2CSA in presence of plCS, DBl1-DBL4,Erythrocyte membrane protein 1
Function / homology
Function and homology information


host cell surface receptor binding / membrane
Similarity search - Function
Plasmodium falciparum erythrocyte membrane protein 1, N-terminal / N-terminal segments of P. falciparum erythrocyte membrane protein / 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
Similarity search - Component
Biological speciesPlasmodium falciparum (malaria parasite P. falciparum)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.1 Å
AuthorsWang KT / Dagil R / Gourdon PE / Salanti A
CitationJournal: Nat Commun / Year: 2021
Title: Cryo-EM reveals the architecture of placental malaria VAR2CSA and provides molecular insight into chondroitin sulfate binding.
Authors: Kaituo Wang / Robert Dagil / Thomas Lavstsen / Sandeep K Misra / Charlotte B Spliid / Yong Wang / Tobias Gustavsson / Daniel R Sandoval / Elena Ethel Vidal-Calvo / Swati Choudhary / Mette Ø ...Authors: Kaituo Wang / Robert Dagil / Thomas Lavstsen / Sandeep K Misra / Charlotte B Spliid / Yong Wang / Tobias Gustavsson / Daniel R Sandoval / Elena Ethel Vidal-Calvo / Swati Choudhary / Mette Ø Agerbaek / Kresten Lindorff-Larsen / Morten A Nielsen / Thor G Theander / Joshua S Sharp / Thomas Mandel Clausen / Pontus Gourdon / Ali Salanti /
Abstract: Placental malaria can have severe consequences for both mother and child and effective vaccines are lacking. Parasite-infected red blood cells sequester in the placenta through interaction between ...Placental malaria can have severe consequences for both mother and child and effective vaccines are lacking. Parasite-infected red blood cells sequester in the placenta through interaction between parasite-expressed protein VAR2CSA and the glycosaminoglycan chondroitin sulfate A (CS) abundantly present in the intervillous space. Here, we report cryo-EM structures of the VAR2CSA ectodomain at up to 3.1 Å resolution revealing an overall V-shaped architecture and a complex domain organization. Notably, the surface displays a single significantly electropositive patch, compatible with binding of negatively charged CS. Using molecular docking and molecular dynamics simulations as well as comparative hydroxyl radical protein foot-printing of VAR2CSA in complex with placental CS, we identify the CS-binding groove, intersecting with the positively charged patch of the central VAR2CSA structure. We identify distinctive conserved structural features upholding the macro-molecular domain complex and CS binding capacity of VAR2CSA as well as divergent elements possibly allowing immune escape at or near the CS binding site. These observations will support rational design of second-generation placental malaria vaccines.
History
DepositionDec 3, 2020-
Header (metadata) releaseJun 2, 2021-
Map releaseJun 2, 2021-
UpdateMay 25, 2022-
Current statusMay 25, 2022Processing site: PDBe / Status: Released

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Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 0.5
  • Imaged by UCSF Chimera
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  • Surface view colored by radius
  • Surface level: 0.5
  • Imaged by UCSF Chimera
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  • Surface view with fitted model
  • Atomic models: PDB-7b54
  • Surface level: 0.5
  • Imaged by UCSF Chimera
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Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

emd_12018.png

Downloads & links

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Map

FileDownload / File: emd_12018.map.gz / Format: CCP4 / Size: 325 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Voxel sizeX=Y=Z: 0.83 Å
Density
Contour LevelBy AUTHOR: 0.5 / Movie #1: 0.5
Minimum - Maximum-0.895538 - 2.3403275
Average (Standard dev.)-0.0012846472 (±0.04320797)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions440440440
Spacing440440440
CellA=B=C: 365.19998 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z0.830.830.83
M x/y/z440440440
origin x/y/z0.0000.0000.000
length x/y/z365.200365.200365.200
α/β/γ90.00090.00090.000
start NX/NY/NZ000
NX/NY/NZ400400400
MAP C/R/S123
start NC/NR/NS000
NC/NR/NS440440440
D min/max/mean-0.8962.340-0.001

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Supplemental data

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Sample components

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Entire : VAR2CSA in presence of plCS, DBl1-DBL4

EntireName: VAR2CSA in presence of plCS, DBl1-DBL4
Components
  • Complex: VAR2CSA in presence of plCS, DBl1-DBL4
    • Protein or peptide: VAR2CSA in presence of plCS, DBl1-DBL4,Erythrocyte membrane protein 1

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Supramolecule #1: VAR2CSA in presence of plCS, DBl1-DBL4

SupramoleculeName: VAR2CSA in presence of plCS, DBl1-DBL4 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Plasmodium falciparum (malaria parasite P. falciparum)
Recombinant expressionOrganism: Trichoplusia ni (cabbage looper)

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Macromolecule #1: VAR2CSA in presence of plCS, DBl1-DBL4,Erythrocyte membrane protein 1

MacromoleculeName: VAR2CSA in presence of plCS, DBl1-DBL4,Erythrocyte membrane protein 1
type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Plasmodium falciparum (malaria parasite P. falciparum)
Molecular weightTheoretical: 219.438562 KDa
Recombinant expressionOrganism: Trichoplusia ni (cabbage looper)
SequenceString: MDSTSTIANK IEEYLGAKSD DSKIDELLKA DPSEVEYYRS GGDGDYLKNN ICKITVNHSD SGKYDPCEKK LPPYDDNDQW KCQQNSSDG SGKPENICVP PRRERLCTYN LENLKFDKIR DNNAFLADVL LTARNEGEKI VQNHPDTNSS NVCNALERSF A DLADIIRG ...String:
MDSTSTIANK IEEYLGAKSD DSKIDELLKA DPSEVEYYRS GGDGDYLKNN ICKITVNHSD SGKYDPCEKK LPPYDDNDQW KCQQNSSDG SGKPENICVP PRRERLCTYN LENLKFDKIR DNNAFLADVL LTARNEGEKI VQNHPDTNSS NVCNALERSF A DLADIIRG TDQWKGTNSN LEKNLKQMFA KIRENDKVLQ DKYPKDQKYT KLREAWWNAN RQKVWEVITC GARSNDLLIK RG WRTSGKS DRKKNFELCR KCGHYEKEVP TKLDYVPQFL RWLTEWIEDF YREKQNLIDD MERHREECTR EDHKSKEGTS YCS TCKDKC KKYCECVKKW KTEWENQENK YKDLYEQNKN KTSQKNTSRY DDYVKDFFEK LEANYSSLEN YIKGDPYFAE YATK LSFIL NPSDGILQEN CSDNKRGSSS NDSCDNKNQD ECQKKLEKVF ASLTNGYKCD KCKSGTSRSK KKWIWKKSSG NEEGL QEEY ANTIGLPPRT QSLYLGNLPK LENVCEDVKD INFDTKEKFL AGCLIVSFHE GKNLKKRYPQ NKNSGNKENL CKALEY SFA DYGDLIKGTS IWDNEYTKDL ELNLQNNFGK LFGKYIKKNN TAEQDTSYSS LDELRESWWN TNKKYIWTAM KHGAEMN IT TCNADGSVTG SGSSCDDIPT IDLIPQYLRF LQEWVENFCE QRQAKVKDVI TNCKSCKESG NKCKTECKTK CKDECEKY K KFIEACGTAG GGIGTAGSPW SKRWDQIYKR YSKHIEDAKR NRKAGTKNCG TSSTTNAAAS TDENKCVQSD IDSFFKHLI DIGLTTPSSY LSNVLDDNIC GADKAPWTTY TTYTTTEKCN KERDKSKSQS SDTLVVVNVP SPLGNTPYRY KYACQCKIPT NEETCDDRK EYMNQWSCGS ARTMKRGYKN DNYELCKYNG VDVKPTTVRS NSSKLDGNDV TFFNLFEQWN KEIQYQIEQY M TNANISCI DEKEVLDSVS DEGTPKVRGG YEDGRNNNTD QGTNCKEKCK CYKLWIEKIN DQWGKQKDNY NKFRSKQIYD AN KGSQNKK VVSLSNFLFF SCWEEYIQKY FNGDWSKIKN IGSDTFEFLI KKCGNNSAHG EEIFSEKLKN AEKKCKENES TDT NINKSE TSCDLNATNY IRGCQSKTYD GKIFPGKGGE KQWICKDTII HGDTNGACIP PRTQNLCVGE LWDKSYGGRS NIKN DTKEL LKEKIKNAIH KETELLYEYH DTGTAIISKN DKKGQKGKND PNGLPKGFCH AVQRSFIDYK NMILGTSVNI YEHIG KLQE DIKKIIEKGT PQQKDKIGGV GSSTENVNAW WKGIEREMWD AVRCAITKIN KKNNNSIFNG DECGVSPPTG NDEDQS VSW FKEWGEQFCI ERLRYEQNIR EACTINGKNE KKCINSKSGQ GDKIQGACKR KCEKYKKYIS EKKQEWDKQK TKYENKY VG KSASDLLKEN YPECISANFD FIFNDNIEYK TYYPYGDYSS ICSCEQVKYY KYNNAEKKNN KSLCYEKDND MTWSKKYI K KLENGRSLEG VYVPPRRQQL CLYELFPIII KNEEGMEKAK EELLETLQIV AEREAYYLWK QYNPTGKGID DANKKACCA IRGSFYDLED IIKGNDLVHD EYTKYIDSKL NEIFGSSNTN DIDTKRARTD WWENETITNG TDRKTIRQLV WDAMQSGVRY AVEEKNENF PLCMGVEHIG IAKPQFIRWL EEWTNEFCEK YTKYFEDMKS KCDPPKRADT CGDNSNIECK KACANYTNWL N PKRIEWNG MSNYYNKIYR KSNKESEDGK DYSMIMAPTV IDYLNKRCHG EINGNYICCS CKNIGAYNTT SGTVNKKLQK KE TECEEEK GPLDLMNEVL NKMDKKYSAH KMKCTEVYLE HVEEQLNEID NAIKDYKL

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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: 7.5 / Details: 20mM Tris pH 7.5 and 75mM KCl
GridModel: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 300 / Pretreatment - Type: GLOW DISCHARGE
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: FEI FALCON III (4k x 4k) / Detector mode: COUNTING / Average electron dose: 40.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsC2 aperture diameter: 100.0 µm / Illumination mode: OTHER / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm
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: 1022972
CTF correctionSoftware - Name: cryoSPARC
Final reconstructionNumber classes used: 1 / Applied symmetry - Point group: C1 (asymmetric) / Algorithm: BACK PROJECTION / Resolution.type: BY AUTHOR / Resolution: 3.1 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 266774
Initial angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC
Final angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC
Final 3D classificationNumber classes: 1 / Software - Name: cryoSPARC
FSC plot (resolution estimation)

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Atomic model buiding 1

RefinementProtocol: AB INITIO MODEL
Output model

PDB-7b54:
VAR2CSA full ectodomain in present of plCS, DBL1-DBL4

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