Identification of the binding domain of Plasmodium falciparum erythrocyte binding protein.

恶性疟原虫红细胞结合蛋白结合域的鉴定。

• 批准号: 16390126
• 负责人: TORII Motomi
• 金额: $ 9.66万
• 依托单位: Ehime University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390126/
• 关键词: infectious disease; malaria; Plasmodium; マラリア; 熱帯熱マラリア原虫; 赤血球結合; 遺伝子組換え; 緑色蛍光蛋白質

Invasive form of Plasmodium falciparum malaria parasite possesses microorganelle, called Rhoptry, at its apex, from which erythrocyte binding protein RhopH complex (comprising RhopH1, RhopH2, and RhopH3) is discharged and considered to have essential role, because of the failure of attempt to disrupt gene locus. We showed that this complex binds erythrocyte surface via protein and GPI-anchor dependent manner, but the precise mechanism is still unknown. Thus, in this project, we generated genetically manipulated Plasmodium falciparum, which express a part of RhopH complex fused with GFP and asked if each chimeric protein have erythrocyte binding ability. To this end, we generated 4 parasite lines possessing plasmids which would express 1/3 of RhopH1, 2/3 of RhopH1, full length of RhopH1 fused with GFP, or GFP alone under the rhoptry protein promoter. However, we could observe GFP signal only from parasite for 1/3 of RhopH1 and GFP only. The reason why GFP signal is not detected from parasites with 2/3 or full length of RhopH1 is unknown, but we speculate that this maybe because of the relatively large plasmid size. Interestingly, parasite expressing GFP fused with only signal peptide of the RhopH2 showed rhoptry localization of GFP. This indicates that the default destination of the protein with signal peptide could be rhoptry among multipel microorganelle. Immunoprecipitation against RhopH2 did not co-purify 1/3 of RhopH1 plus GFP, indicating this part is not responsible for the RhopH complex formation. Also, we could not observe erythrocyte binding ability for this 1/3 of RhopH1 chimeric protein, suggesting that this region may not be the binding domain.

恶性疟原虫疟疾寄生虫的侵入形式在其顶端具有称为Rhoptry的微细胞器，红细胞结合蛋白RhopH复合物（包括RhopH 1、RhopH 2和RhopH 3）从其中排出，并被认为具有重要作用，因为破坏基因座的尝试失败了。我们发现该复合物通过蛋白质和GPI锚定依赖的方式结合红细胞表面，但其确切机制尚不清楚。因此，在本项目中，我们产生了基因操纵的恶性疟原虫，其表达与GFP融合的RhopH复合物的一部分，并询问每个嵌合蛋白是否具有红细胞结合能力。为此，我们产生了4种具有质粒的寄生虫系，所述质粒在棒状蛋白启动子下表达1/3的RhopH 1、2/3的RhopH 1、与GFP融合的全长RhopH 1或单独的GFP。然而，我们只能观察到GFP信号从寄生虫的1/3的RhopH 1和GFP只有。在RhopH 1的2/3或全长的寄生虫中未检测到GFP信号的原因尚不清楚，但我们推测这可能是因为相对较大的质粒大小。有趣的是，表达仅与RhopH 2的信号肽融合的GFP的寄生虫显示GFP的棒状体定位。这表明，信号肽的蛋白质的默认目的地可能是多细胞器之间的棒状体。针对RhopH 2的免疫沉淀没有共纯化1/3的RhopH 1加GFP，表明该部分不负责RhopH复合物的形成。此外，我们无法观察到RhopH 1嵌合蛋白的这1/3的红细胞结合能力，这表明该区域可能不是结合结构域。

项目成果

Antibodies against MAEBL ligand domains M1 and M2 inhibit sporozoite development in vitro

• DOI: 10.1128/iai.72.6.3604-3608.2004
• 发表时间: 2004-06-01
• 期刊: INFECTION AND IMMUNITY
• 影响因子: 3.1
• 作者: Preiser, P;Rénia, L;Adams, JH
• 通讯作者: Adams, JH

2-Cys peroxiredoxin TPx-1 is involved in gametocyte development in Plasmodium berghei

• DOI: 10.1016/j.molbiopara.2006.02.018
• 发表时间: 2006-07-01
• 期刊: MOLECULAR AND BIOCHEMICAL PARASITOLOGY
• 影响因子: 1.5
• 作者: Yano, Kazuhiko;Komaki-Yasuda, Kanako;Kawazu, Shin-ichiro
• 通讯作者: Kawazu, Shin-ichiro

Nasal immunization with a malaria transmission-blocking vaccine candidate Pfs25 induces complete protective immunity in mice against field-isolated Plasmodium falciparum

使用阻断疟疾传播的候选疫苗 Pfs25 进行鼻免疫可诱导小鼠针对现场隔离的恶性疟原虫产生完全保护性免疫力

• 发表时间: 2005
• 期刊: Infection and Immunity 73
• 作者: Arakawa T;et. al.
• 通讯作者: et. al.

The Plasmodium falciparum clag 9 gene encodes a rhoptry protein.

恶性疟原虫 clag 9 基因编码一种菱形蛋白。

• 发表时间: 2004
• 期刊: Mol Microb 52(1)
• 作者: Ishii T.;Yasuda K.;Akatsuka A.;Hino O.;Hartman P.S.;Ishii N.;Kaneko O et al.;Winter G et al.;Hino O.;Arakawa T et al.;Rungruang T et al.;Ling IT et al.
• 通讯作者: Ling IT et al.

SURFIN is a polymorphic antigen expressed on Plasmodium falciparum merozoites and infected erythrocytes.

Surfin是一种在恶性疟原虫植物和感染的红细胞上表达的多态性抗原。

• DOI: 10.1084/jem.20041392
• 发表时间: 2005-06-06
• 期刊: JOURNAL OF EXPERIMENTAL MEDICINE
• 影响因子: 15.3
• 作者: Winter, G;Kawai, S;Haeggström, M;Kaneko, O;von Euler, A;Kawazu, SI;Palm, D;Fernandez, V;Wahlgren, M
• 通讯作者: Wahlgren, M