5f3j
From Proteopedia
Crystal structure of DBP in complex with inhibitory monoclonal antibody 2D10
Structural highlights
FunctionPVDR_PLAVS Binds to the human erythrocytes Duffy blood group determinant. Publication Abstract from PubMedPlasmodium 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. Broadly neutralizing epitopes in the Plasmodium vivax vaccine candidate Duffy Binding Protein.,Chen E, Salinas ND, Huang Y, Ntumngia F, Plasencia MD, Gross ML, Adams JH, Tolia NH Proc Natl Acad Sci U S A. 2016 May 18. pii: 201600488. PMID:27194724[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also
References
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