Pfs47, paralog of the male fertility factor Pfs48/45, is a female specitic surface protein in Plasmodium falciparum

Pfs47, paralog of the male fertility factor Pfs48/45, is a female specitic surface protein in Plasmodium falciparum
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DOI:
10.1016/j.molbiopara.2006.05.015
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发表时间:
2006-10-01
影响因子:
1.5
通讯作者:
Sauerwein, Robert W.
Sauerwein, Robert W.
中科院分区:
医学4区
文献类型:
--
作者:
van Schaijk, Ben C. L.;van Dijk, Melissa R.;Sauerwein, Robert W.

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恶性疟原虫基因组包含一个小基因家族,表达以6-半胱氨酸结构域为特征的蛋白质。这些蛋白质大部分表达在寄生虫的表面,一些已知在细胞与细胞之间的相互作用中发挥作用。该家族的两个成员,Pfs48/45和Pfs230,形成一个位于配子表面的复合体,被认为是传播阻断疫苗的重要靶点。在这项研究中,我们报告了这个家族的另一个成员Pfs47的分析,Pfs47是Pfs48/45的最接近的平行序列。我们证明Pfs47只在雌配子细胞中表达,并且在从红细胞中出现后定位于雌配子的表面。与P48/45对男性生育的关键功能相反,Pfs47似乎对女性生育并不是至关重要的。通过定向基因破坏而缺乏Pfs47的寄生虫,当包括在蚊子媒介的血餐中时,会产生正常数量的卵囊。此外,三种抗Pfs47的单抗在含有野生型寄生虫的血粉中不能抑制卵囊的发育。这些结果表明Pfs47的蛋白质功能存在冗余,并减少了对Pfs47作为传播阻断疫苗靶点的支持。(C)2006爱思唯尔B.V.保留所有权利。
The genome of Plasmodium falciparum contains a small gene family that expresses proteins characterized by the presence of 6-cysteine domains. Most of these proteins are expressed on the surface of the parasite and some are known to play a role in cell-cell interactions. Two members of this family, Pfs48/45 and Pfs230, form a complex localized on the surface of gametes and are recognized as important targets for transmission-blocking vaccines. In this study we report the analysis of an additional member of this family, Pfs47 the closest paralog of Pfs48/45. We demonstrate that Pfs47 is expressed only in female gametocytes and is located on the surface of female gametes following emergence from red blood cells. In contrast to the critical function of P48/45 for male fertility, Pfs47 does not appear crucial for female fertility. Parasites lacking Pfs47 through targeted gene disruption, produce normal numbers of oocysts when included in the blood meal of the mosquito vector. In addition, three monoclonal antibodies against Pfs47 were unable to inhibit oocyst development when present in a blood meal containing wild type parasites. These results show redundancy in protein function for Pfs47 and reduce the support for candidacy of Pfs47 as a transmission-blocking vaccine target. (c) 2006 Elsevier B.V. All rights reserved.