5F3J

Crystal structure of DBP in complex with inhibitory monoclonal antibody 2D10

Summary for 5F3J

• Entry DOI: 10.2210/pdb5f3j/pdb
• Descriptor: Duffy receptor, Antibody 2D10 single chain variable fragment (2 entities in total)
• Functional Keywords: plasmodium, vivax, duffy binding protein, dbp, antibody, malaria, scfv, neutralizing, interaction, immune, blocking, invasion, vaccine, therapeutic, immune system
• Biological source: Plasmodium vivax (strain Salvador I); More
• Total number of polymer chains: 4
• Total formula weight: 139676.00

Authors

Chen, E.,Salinas, N.D.,Tolia, N.H. (deposition date: 2015-12-02, release date: 2016-05-18, Last modification date: 2024-11-13)

Primary citation

Chen, E.,Salinas, N.D.,Huang, Y.,Ntumngia, F.,Plasencia, M.D.,Gross, M.L.,Adams, J.H.,Tolia, N.H.
Broadly neutralizing epitopes in the Plasmodium vivax vaccine candidate Duffy Binding Protein.
Proc.Natl.Acad.Sci.USA, 113:6277-6282, 2016

PubMed Abstract: Plasmodium vivax Duffy Binding Protein (PvDBP) is the most promising vaccine candidate for P. vivax malaria. The polymorphic nature of PvDBP induces strain-specific immune responses, however, and the epitopes of broadly neutralizing antibodies are unknown. These features hamper the rational design of potent DBP-based vaccines and necessitate the identification of globally conserved epitopes. Using X-ray crystallography, small-angle X-ray scattering, hydrogen-deuterium exchange mass spectrometry, and mutational mapping, we have defined epitopes for three inhibitory mAbs (mAbs 2D10, 2H2, and 2C6) and one noninhibitory mAb (3D10) that engage DBP. These studies expand the currently known inhibitory epitope repertoire by establishing protective motifs in subdomain three outside the receptor-binding and dimerization residues of DBP, and introduce globally conserved protective targets. All of the epitopes are highly conserved among DBP alleles. The identification of broadly conserved epitopes of inhibitory antibodies provides critical motifs that should be retained in the next generation of potent vaccines for P. vivax malaria.

PubMed: 27194724
DOI: 10.1073/pnas.1600488113

Experimental method

X-RAY DIFFRACTION (4.001 Å)