[English] 日本語
Yorodumi
- EMDB-28135: Cryo-EM structure of L9 Fab in complex with rsCSP -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-28135
TitleCryo-EM structure of L9 Fab in complex with rsCSP
Map dataCryo-EM structure of L9 Fab in complex with rsCSP
Sample
  • Complex: trimeric complex of L9 Fab with rsCSP
    • Complex: Circumsporozoite protein
      • Protein or peptide: Circumsporozoite protein
    • Complex: L9 Heavy chain, L9 Light chain
      • Protein or peptide: L9 Heavy chain
      • Protein or peptide: L9 Light chain
KeywordsPfCSP / malaria / antibody / IMMUNE SYSTEM
Function / homology
Function and homology information


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 speciesPlasmodium falciparum (malaria parasite P. falciparum) / Homo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.36 Å
AuthorsMartin GM / Ward AB
Funding support United States, 1 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID) United States
CitationJournal: Nat Commun / Year: 2023
Title: Structural basis of epitope selectivity and potent protection from malaria by PfCSP antibody L9.
Authors: Gregory M Martin / Monica L Fernández-Quintero / Wen-Hsin Lee / Tossapol Pholcharee / Lisa Eshun-Wilson / Klaus R Liedl / Marie Pancera / Robert A Seder / Ian A Wilson / Andrew B Ward /
Abstract: A primary objective in malaria vaccine design is the generation of high-quality antibody responses against the circumsporozoite protein of the malaria parasite, Plasmodium falciparum (PfCSP). To ...A primary objective in malaria vaccine design is the generation of high-quality antibody responses against the circumsporozoite protein of the malaria parasite, Plasmodium falciparum (PfCSP). To enable rational antigen design, we solved a cryo-EM structure of the highly potent anti-PfCSP antibody L9 in complex with recombinant PfCSP. We found that L9 Fab binds multivalently to the minor (NPNV) repeat domain, which is stabilized by a unique set of affinity-matured homotypic, antibody-antibody contacts. Molecular dynamics simulations revealed a critical role of the L9 light chain in integrity of the homotypic interface, which likely impacts PfCSP affinity and protective efficacy. These findings reveal the molecular mechanism of the unique NPNV selectivity of L9 and emphasize the importance of anti-homotypic affinity maturation in protective immunity against P. falciparum.
History
DepositionSep 13, 2022-
Header (metadata) releaseJun 28, 2023-
Map releaseJun 28, 2023-
UpdateJun 28, 2023-
Current statusJun 28, 2023Processing site: RCSB / Status: Released

-
Structure visualization

Supplemental images

emd_28135.png

Downloads & links

-
Map

FileDownload / File: emd_28135.map.gz / Format: CCP4 / Size: 22.2 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationCryo-EM structure of L9 Fab in complex with rsCSP
Voxel sizeX=Y=Z: 1.045 Å
Density
Contour LevelBy EMDB: 0.328
Minimum - Maximum-1.4126118 - 1.9824775
Average (Standard dev.)0.003382 (±0.06406674)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions180180180
Spacing180180180
CellA=B=C: 188.09999 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Half map: Cryo-EM structure of L9 Fab in complex with rsCSP

Fileemd_28135_half_map_1.map
AnnotationCryo-EM structure of L9 Fab in complex with rsCSP
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: Cryo-EM structure of L9 Fab in complex with rsCSP

Fileemd_28135_half_map_2.map
AnnotationCryo-EM structure of L9 Fab in complex with rsCSP
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : trimeric complex of L9 Fab with rsCSP

EntireName: trimeric complex of L9 Fab with rsCSP
Components
  • Complex: trimeric complex of L9 Fab with rsCSP
    • Complex: Circumsporozoite protein
      • Protein or peptide: Circumsporozoite protein
    • Complex: L9 Heavy chain, L9 Light chain
      • Protein or peptide: L9 Heavy chain
      • Protein or peptide: L9 Light chain

-
Supramolecule #1: trimeric complex of L9 Fab with rsCSP

SupramoleculeName: trimeric complex of L9 Fab with rsCSP / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all

-
Supramolecule #2: Circumsporozoite protein

SupramoleculeName: Circumsporozoite protein / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1
Source (natural)Organism: Plasmodium falciparum (malaria parasite P. falciparum)

-
Supramolecule #3: L9 Heavy chain, L9 Light chain

SupramoleculeName: L9 Heavy chain, L9 Light chain / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2-#3
Source (natural)Organism: Homo sapiens (human)

-
Macromolecule #1: Circumsporozoite protein

MacromoleculeName: Circumsporozoite protein / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Plasmodium falciparum (malaria parasite P. falciparum)
Molecular weightTheoretical: 30.363354 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString: MYGSSSNTRV LNELNYDNAG TNLYNELEMN YYGKQENWYS LKKNSRSLGE NDDGNNEDNE KLRKPKHKKL KQPADGNPDP NANPNVDPN ANPNVDPNAN PNVDPNANPN ANPNANPNAN PNANPNANPN ANPNANPNAN PNANPNANPN ANPNANPNAN P NANPNANP ...String:
MYGSSSNTRV LNELNYDNAG TNLYNELEMN YYGKQENWYS LKKNSRSLGE NDDGNNEDNE KLRKPKHKKL KQPADGNPDP NANPNVDPN ANPNVDPNAN PNVDPNANPN ANPNANPNAN PNANPNANPN ANPNANPNAN PNANPNANPN ANPNANPNAN P NANPNANP NKNNQGNGQG HNMPNDPNRN VDENANANSA VKNNNNEEPS DKHIKEYLNK IQNSLSTEWS PCSVTCGNGI QV RIKPGSA NKPKDELDYA NDIEKKICKM EKCSSVFNVV NS

-
Macromolecule #2: L9 Heavy chain

MacromoleculeName: L9 Heavy chain / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 24.475436 KDa
Recombinant expressionOrganism: Cricetulus griseus (Chinese hamster)
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 #3: L9 Light chain

MacromoleculeName: L9 Light chain / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 23.597254 KDa
Recombinant expressionOrganism: Cricetulus griseus (Chinese hamster)
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

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

BufferpH: 7.4
VitrificationCryogen name: ETHANE

-
Electron microscopy

MicroscopeFEI TITAN KRIOS
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.9 µm
Image recordingFilm or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Average electron dose: 60.0 e/Å2
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

-
Image processing

Startup modelType of model: OTHER
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: PROJECTION MATCHING
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.36 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 451712

+
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