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Structure paper

タイトル	Cryo-EM structure of an essential Plasmodium vivax invasion complex.
ジャーナル・号・ページ	Nature, Vol. 559, Issue 7712, Page 135-139, Year 2018
掲載日	2018年6月27日
著者	Jakub Gruszczyk / Rick K Huang / Li-Jin Chan / Sébastien Menant / Chuan Hong / James M Murphy / Yee-Foong Mok / Michael D W Griffin / Richard D Pearson / Wilson Wong / Alan F Cowman / Zhiheng Yu / Wai-Hong Tham /
PubMed 要旨	Plasmodium vivax is the most widely distributed malaria parasite that infects humans. P. vivax invades reticulocytes exclusively, and successful entry depends on specific interactions between the P. ...Plasmodium vivax is the most widely distributed malaria parasite that infects humans. P. vivax invades reticulocytes exclusively, and successful entry depends on specific interactions between the P. vivax reticulocyte-binding protein 2b (PvRBP2b) and transferrin receptor 1 (TfR1). TfR1-deficient erythroid cells are refractory to invasion by P. vivax, and anti-PvRBP2b monoclonal antibodies inhibit reticulocyte binding and block P. vivax invasion in field isolates. Here we report a high-resolution cryo-electron microscopy structure of a ternary complex of PvRBP2b bound to human TfR1 and transferrin, at 3.7 Å resolution. Mutational analyses show that PvRBP2b residues involved in complex formation are conserved; this suggests that antigens could be designed that act across P. vivax strains. Functional analyses of TfR1 highlight how P. vivax hijacks TfR1, an essential housekeeping protein, by binding to sites that govern host specificity, without affecting its cellular function of transporting iron. Crystal and solution structures of PvRBP2b in complex with antibody fragments characterize the inhibitory epitopes. Our results establish a structural framework for understanding how P. vivax reticulocyte-binding protein engages its receptor and the molecular mechanism of inhibitory monoclonal antibodies, providing important information for the design of novel vaccine candidates.
リンク	Nature / PubMed:29950717
手法	EM (単粒子) / X線回折
解像度	1.87 - 3.8 Å
構造データ	7783 6d03 EMDB-7783, PDB-6d03: Cryo-EM structure of a Plasmodium vivax invasion complex essential for entry into human reticulocytes; one molecule of parasite ligand. 手法: EM (単粒子) / 解像度: 3.68 Å 7784 6d04 EMDB-7784, PDB-6d04: Cryo-EM structure of a Plasmodium vivax invasion complex essential for entry into human reticulocytes; two molecules of parasite ligand, subclass 1. 手法: EM (単粒子) / 解像度: 3.74 Å 7785 6d05 EMDB-7785, PDB-6d05: Cryo-EM structure of a Plasmodium vivax invasion complex essential for entry into human reticulocytes; two molecules of parasite ligand, subclass 2. 手法: EM (単粒子) / 解像度: 3.8 Å PDB-6bpa: Plasmodium vivax reticulocyte binding protein 2b (PvRBP2b) bound to monoclonal antibody 3E9 手法: X-RAY DIFFRACTION / 解像度: 2.53 Å PDB-6bpb: Plasmodium vivax invasion blocking monoclonal antibody 4F7 手法: X-RAY DIFFRACTION / 解像度: 1.87 Å PDB-6bpc: Plasmodium vivax reticulocyte binding protein 2b (PvRBP2b) bound to monoclonal antibody 4F7 手法: X-RAY DIFFRACTION / 解像度: 2.66 Å PDB-6bpd: Plasmodium vivax invasion blocking monoclonal antibody 10B12 手法: X-RAY DIFFRACTION / 解像度: 2.32 Å PDB-6bpe: Plasmodium vivax reticulocyte binding protein 2b (PvRBP2b) bound to monoclonal antibody 6H1 手法: X-RAY DIFFRACTION / 解像度: 3.34 Å
化合物	ChemComp-BR: BROMIDE ION / ブロミド / 臭化物 ChemComp-HOH: WATER / 水 ChemComp-CA: Unknown entry / カルシウムジカチオン ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose / N-アセチル-β-D-グルコサミン / N-アセチルグルコサミン ChemComp-FE: Unknown entry / 鉄 ChemComp-CO3: CARBONATE ION / 炭酸ジアニオン / 炭酸塩
由来	Homo sapiens (ヒト) Human (ヒト) plasmodium vivax (マラリア病原虫) plasmodium vivax (strain salvador i) (マラリア病原虫) mus musculus (ハツカネズミ)
キーワード	CELL INVASION / Plasmodium vivax / invasion / malaria (マラリア) / antibody complex (抗体) / IMMUNE SYSTEM (免疫系) / antibody (抗体) / reticulocyte (網赤血球)