6x8p

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Crystal structure of 3D11 Fab in complex with Plasmodium berghei circumsporozoite protein NPND peptideCrystal structure of 3D11 Fab in complex with Plasmodium berghei circumsporozoite protein NPND peptide

Structural highlights

6x8p is a 3 chain structure with sequence from Mus musculus and Plasmodium berghei ANKA. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.27Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Publication Abstract from PubMed

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 P. falciparum (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 P. berghei 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.

Structural ordering of the Plasmodium berghei circumsporozoite protein repeats by inhibitory antibody 3D11.,Kucharska I, Thai E, Srivastava A, Rubinstein JL, Pomes R, Julien JP Elife. 2020 Nov 30;9:e59018. doi: 10.7554/eLife.59018. PMID:33253113[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. Kucharska I, Thai E, Srivastava A, Rubinstein JL, Pomès R, Julien JP. Structural ordering of the Plasmodium berghei circumsporozoite protein repeats by inhibitory antibody 3D11. Elife. 2020 Nov 30;9:e59018. PMID:33253113 doi:10.7554/eLife.59018

6x8p, resolution 2.27Å

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OCA