[English] 日本語
Yorodumi
- EMDB-28192: Cryo-EM structure of a potent anti-malarial antibody L9 in comple... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-28192
TitleCryo-EM structure of a potent anti-malarial antibody L9 in complex with Plasmodium falciparum circumsporozoite protein (PfCSP)(dominant class)
Map data
Sample
  • Complex: PfCSP in complex with antibody L9
    • Protein or peptide: L9 Fab heavy chain
    • Protein or peptide: L9 Fab light chain
    • Protein or peptide: Circumsporozoite protein
KeywordsAnti-Malarial / PfCSP / IMMUNE SYSTEM
Function / homology
Function and homology information


host cell surface binding / symbiont entry into host / entry into host cell by a symbiont-containing vacuole / heparan sulfate proteoglycan binding / side of membrane / cell surface / plasma membrane / cytoplasm
Similarity search - Function
: / Plasmodium circumsporozoite protein / Thrombospondin type 1 domain / Thrombospondin type-1 (TSP1) repeat superfamily / Thrombospondin type-1 (TSP1) repeat profile. / Thrombospondin type 1 repeats / Thrombospondin type-1 (TSP1) repeat
Similarity search - Domain/homology
Circumsporozoite protein
Similarity search - Component
Biological speciesHomo sapiens (human) / Plasmodium falciparum 3D7 (eukaryote)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.6 Å
AuthorsTripathi P / Kwong PD
Funding support United States, 1 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID) United States
CitationJournal: Structure / Year: 2023
Title: Cryo-EM structures of anti-malarial antibody L9 with circumsporozoite protein reveal trimeric L9 association and complete 27-residue epitope.
Authors: Prabhanshu Tripathi / Michael F Bender / Haotian Lei / Lais Da Silva Pereira / Chen-Hsiang Shen / Brian Bonilla / Marlon Dillon / Li Ou / Marie Pancera / Lawrence T Wang / Baoshan Zhang / ...Authors: Prabhanshu Tripathi / Michael F Bender / Haotian Lei / Lais Da Silva Pereira / Chen-Hsiang Shen / Brian Bonilla / Marlon Dillon / Li Ou / Marie Pancera / Lawrence T Wang / Baoshan Zhang / Facundo D Batista / Azza H Idris / Robert A Seder / Peter D Kwong /
Abstract: Monoclonal antibody L9 recognizes the Plasmodium falciparum circumsporozoite protein (PfCSP) and is highly protective following controlled human malaria challenge. To gain insight into its function, ...Monoclonal antibody L9 recognizes the Plasmodium falciparum circumsporozoite protein (PfCSP) and is highly protective following controlled human malaria challenge. To gain insight into its function, we determined cryoelectron microscopy (cryo-EM) structures of L9 in complex with full-length PfCSP and assessed how this recognition influenced protection by wild-type and mutant L9s. Cryo-EM reconstructions at 3.6- and 3.7-Å resolution revealed L9 to recognize PfCSP as an atypical trimer. Each of the three L9s in the trimer directly recognized an Asn-Pro-Asn-Val (NPNV) tetrapeptide on PfCSP and interacted homotypically to facilitate L9-trimer assembly. We analyzed peptides containing different repeat tetrapeptides for binding to wild-type and mutant L9s to delineate epitope and homotypic components of L9 recognition; we found both components necessary for potent malaria protection. Last, we found the 27-residue stretch recognized by L9 to be highly conserved in P. falciparum isolates, suggesting the newly revealed complete L9 epitope to be an attractive vaccine target.
History
DepositionSep 19, 2022-
Header (metadata) releaseMar 15, 2023-
Map releaseMar 15, 2023-
UpdateNov 13, 2024-
Current statusNov 13, 2024Processing site: RCSB / Status: Released

-
Structure visualization

Supplemental images

emd_28192.png

Downloads & links

-
Map

FileDownload / File: emd_28192.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.92 Å/pix.
x 320 pix.
= 294.4 Å		0.92 Å/pix.
x 320 pix.
= 294.4 Å		0.92 Å/pix.
x 320 pix.
= 294.4 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.92 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.35
Minimum - Maximum-1.787172 - 2.6156611
Average (Standard dev.)0.000020739815 (±0.047104094)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions320320320
Spacing320320320
CellA=B=C: 294.4 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Half map: #2

Fileemd_28192_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #1

Fileemd_28192_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : PfCSP in complex with antibody L9

EntireName: PfCSP in complex with antibody L9
Components
  • Complex: PfCSP in complex with antibody L9
    • Protein or peptide: L9 Fab heavy chain
    • Protein or peptide: L9 Fab light chain
    • Protein or peptide: Circumsporozoite protein

-
Supramolecule #1: PfCSP in complex with antibody L9

SupramoleculeName: PfCSP in complex with antibody L9 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Homo sapiens (human)

-
Macromolecule #1: L9 Fab heavy chain

MacromoleculeName: L9 Fab heavy chain / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 24.475436 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: QVKLVESGGG VVQPGRSLRL SCEASGFIFS TYGMHWVRQA PGKGLEWVAV IWFDGSNIYY ADSVKGRFTI SRDNSKNTVF MQMDSLRAE DTAVYYCHRN FYDGSGPFDY WGQGTLVTVS SASTKGPSVF PLAPSSKSTS GGTAALGCLV KDYFPEPVTV S WNSGALTS ...String:
QVKLVESGGG VVQPGRSLRL SCEASGFIFS TYGMHWVRQA PGKGLEWVAV IWFDGSNIYY ADSVKGRFTI SRDNSKNTVF MQMDSLRAE DTAVYYCHRN FYDGSGPFDY WGQGTLVTVS SASTKGPSVF PLAPSSKSTS GGTAALGCLV KDYFPEPVTV S WNSGALTS GVHTFPAVLQ SSGLYSLSSV VTVPSSSLGT QTYICNVNHK PSNTKVDKKV EPKSCDKTH

-
Macromolecule #2: L9 Fab light chain

MacromoleculeName: L9 Fab light chain / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 23.597254 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: DIQMTQSPST LSASVGDRVT ITCRASQFIS RWLAWYQQKP GKAPKLLIYK ASSLESGVPS RFSGSGSETH FTLTISSLQP DDVATYYCQ EYTSYGRTFG QGTKVEIKRT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF YPREAKVQWK VDNALQSGNS Q ESVTEQDS ...String:
DIQMTQSPST LSASVGDRVT ITCRASQFIS RWLAWYQQKP GKAPKLLIYK ASSLESGVPS RFSGSGSETH FTLTISSLQP DDVATYYCQ EYTSYGRTFG QGTKVEIKRT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF YPREAKVQWK VDNALQSGNS Q ESVTEQDS KDSTYSLSST LTLSKADYEK HKVYACEVTH QGLSSPVTKS FNRGEC

-
Macromolecule #3: Circumsporozoite protein

MacromoleculeName: Circumsporozoite protein / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Plasmodium falciparum 3D7 (eukaryote) / Strain: isolate 3D7
Molecular weightTheoretical: 37.807488 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: QEYQSYGSSS NTRVLNELNY DNAGTNLYNE LEMNYYGKQE NWYSLSSNSA SLGENDDGNN EDNEKLRKPK HKKLKQPADG NPDPNANPN VDPNANPNVD PNANPNVDPN ANPNANPNAN PNANPNANPN ANPNANPNAN PNANPNANPN ANPNANPNAN P NANPNANP ...String:
QEYQSYGSSS NTRVLNELNY DNAGTNLYNE LEMNYYGKQE NWYSLSSNSA SLGENDDGNN EDNEKLRKPK HKKLKQPADG NPDPNANPN VDPNANPNVD PNANPNVDPN ANPNANPNAN PNANPNANPN ANPNANPNAN PNANPNANPN ANPNANPNAN P NANPNANP NANPNANPNV DPNANPNANP NANPNANPNA NPNANPNANP NANPNANPNA NPNANPNANP NANPNANPNA NP NANPNAN PNANPNKNNQ GNGQGHNMPN DPNRNVDENA NANSAVKNNN NEEPSDKHIK EYLNKIQNSL STEWSPCSVT CGN GIQVRI KPGSANKPKD ELDYANDIEK KICKMEKCS

UniProtKB: Circumsporozoite protein

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

BufferpH: 7.4
GridModel: C-flat-1.2/1.3 / Pretreatment - Type: GLOW DISCHARGE
VitrificationCryogen name: ETHANE / Instrument: FEI VITROBOT MARK IV

-
Electron microscopy

MicroscopeTFS GLACIOS
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 63.7 e/Å2
Electron beamAcceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 1.5 µm / Nominal defocus min: 0.3 µm / Nominal magnification: 45000
Sample stageCooling holder cryogen: NITROGEN

+
Image processing

Startup modelType of model: PDB ENTRY
PDB model - PDB ID:

7rqp

Final reconstructionNumber classes used: 3 / Resolution.type: BY AUTHOR / Resolution: 3.6 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 2964341
Initial angle assignmentType: NOT APPLICABLE
Final angle assignmentType: NOT APPLICABLE
Final 3D classificationNumber classes: 2
FSC plot (resolution estimation)

-
Atomic model buiding 1

RefinementSpace: REAL / Protocol: AB INITIO MODEL / Overall B value: 147.9
Output model

PDB-8ek1:
Cryo-EM structure of a potent anti-malarial antibody L9 in complex with Plasmodium falciparum circumsporozoite protein (PfCSP)(dominant class)

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more