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Structure paper

TitleStructural ordering of the circumsporozoite protein repeats by inhibitory antibody 3D11.
Journal, issue, pagesElife, Vol. 9, Year 2020
Publish dateNov 30, 2020
AuthorsIga Kucharska / Elaine Thai / Ananya Srivastava / John L Rubinstein / Régis Pomès / Jean-Philippe Julien /
PubMed AbstractPlasmodium sporozoites express circumsporozoite protein (CSP) on their surface, an essential protein that contains central repeating motifs. Antibodies targeting this region can neutralize infection, ...Plasmodium sporozoites express circumsporozoite protein (CSP) on their surface, an essential protein that contains central repeating motifs. Antibodies targeting this region can neutralize infection, and the partial efficacy of RTS,S/AS01 - the leading malaria vaccine against (Pf) - has been associated with the humoral response against the repeats. Although structural details of antibody recognition of PfCSP have recently emerged, the molecular basis of antibody-mediated inhibition of other Plasmodium species via CSP binding remains unclear. Here, we analyze the structure and molecular interactions of potent monoclonal antibody (mAb) 3D11 binding to CSP (PbCSP) using molecular dynamics simulations, X-ray crystallography, and cryoEM. We reveal that mAb 3D11 can accommodate all subtle variances of the PbCSP repeating motifs, and, upon binding, induces structural ordering of PbCSP through homotypic interactions. Together, our findings uncover common mechanisms of antibody evolution in mammals against the CSP repeats of Plasmodium sporozoites.
External linksElife / PubMed:33253113 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution1.55 - 3.2 Å
Structure data

22089

6x87

EMDB-22089, PDB-6x87:
CryoEM structure of the Plasmodium berghei circumsporozoite protein in complex with inhibitory mouse antibody 3D11.
Method: EM (single particle) / Resolution: 3.2 Å

PDB-6x8p:
Crystal structure of 3D11 Fab in complex with Plasmodium berghei circumsporozoite protein NPND peptide
Method: X-RAY DIFFRACTION / Resolution: 2.27 Å

PDB-6x8q:
Crystal structure of 3D11 Fab in complex with Plasmodium berghei circumsporozoite protein PAPP peptide
Method: X-RAY DIFFRACTION / Resolution: 1.6 Å

PDB-6x8s:
Crystal structure of 3D11 Fab in complex with Plasmodium berghei circumsporozoite protein NAND peptide
Method: X-RAY DIFFRACTION / Resolution: 1.55 Å

PDB-6x8u:
Crystal structure of 3D11 Fab in complex with Plasmodium berghei circumsporozoite protein Mixed peptide
Method: X-RAY DIFFRACTION / Resolution: 1.55 Å

Chemicals

ChemComp-EDO:
1,2-ETHANEDIOL / Ethylene glycol

ChemComp-HOH:
WATER / Water

ChemComp-GOL:
GLYCEROL / Glycerol

Source
  • mus musculus (house mouse)
  • Plasmodiidae sp. (eukaryote)
  • plasmodium berghei (eukaryote)
  • plasmodium berghei anka (eukaryote)
KeywordsIMMUNE SYSTEM / antibody / malaria

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