6X8S

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

Summary for 6X8S

• Entry DOI: 10.2210/pdb6x8s/pdb
• Descriptor: 3D11 Fab heavy chain, 3D11 Fab light chain, NAND peptide, ... (5 entities in total)
• Functional Keywords: malaria, antibody, immune system
• Biological source: Mus musculus (Mouse); More
• Total number of polymer chains: 3
• Total formula weight: 49918.65

Authors

Thai, E.,Julien, J.P. (deposition date: 2020-06-01, release date: 2020-12-02, Last modification date: 2024-11-20)

Primary citation

Kucharska, I.,Thai, E.,Srivastava, A.,Rubinstein, J.L.,Pomes, R.,Julien, J.P.
Structural ordering of the Plasmodium berghei circumsporozoite protein repeats by inhibitory antibody 3D11.
Elife, 9:-, 2020

PubMed Abstract: 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.

PubMed: 33253113
DOI: 10.7554/eLife.59018

Experimental method

X-RAY DIFFRACTION (1.55 Å)