5F3J

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

5F3J の概要

• エントリーDOI: 10.2210/pdb5f3j/pdb
• 分子名称: Duffy receptor, Antibody 2D10 single chain variable fragment (2 entities in total)
• 機能のキーワード: plasmodium, vivax, duffy binding protein, dbp, antibody, malaria, scfv, neutralizing, interaction, immune, blocking, invasion, vaccine, therapeutic, immune system
• 由来する生物種: Plasmodium vivax (strain Salvador I); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 139676.00

構造登録者

Chen, E.,Salinas, N.D.,Tolia, N.H. (登録日: 2015-12-02, 公開日: 2016-05-18, 最終更新日: 2024-11-13)

主引用文献

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

実験手法

X-RAY DIFFRACTION (4.001 Å)