- PDB-6x8s: Crystal structure of 3D11 Fab in complex with Plasmodium berghei ... -
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Basic information
Entry
Database: PDB / ID: 6x8s
Title
Crystal structure of 3D11 Fab in complex with Plasmodium berghei circumsporozoite protein NAND peptide
Components
3D11 Fab heavy chain
3D11 Fab light chain
NAND peptide
Keywords
IMMUNE SYSTEM / Malaria / Antibody
Function / homology
Function and homology information
positive regulation by symbiont of entry into host / positive regulation of development of symbiont in host / positive regulation of developmental process / adhesion of symbiont to host cell / entry into host cell by a symbiont-containing vacuole / external side of plasma membrane / cytoplasm Similarity search - Function
National Institutes of Health/National Cancer Institute (NIH/NCI)
ACB-12002
United States
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
AGM-12006
United States
CIFAR Azrieli Global Scholar
Canada
Ontario Early Researcher Award
Canada
Canada Research Chair
Canada
Citation
Journal: Elife / Year: 2020 Title: Structural ordering of the circumsporozoite protein repeats by inhibitory antibody 3D11. Authors: Iga Kucharska / Elaine Thai / Ananya Srivastava / John L Rubinstein / Régis Pomès / Jean-Philippe Julien / 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, ...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.
Mass: 22629.295 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Production host: Homo sapiens (human)
#2: Antibody
3D11Fablightchain
Mass: 23989.838 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Production host: Homo sapiens (human)
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