Reticulocyte-binding protein homologue 5-An essential adhesin involved in invasion of human erythrocytes by Plasmodium falciparum

Reticulocyte-binding protein homologue 5-An essential adhesin involved in invasion of human erythrocytes by Plasmodium falciparum
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DOI:
10.1016/j.ijpara.2008.10.006
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发表时间:
2009-02-01
影响因子:
4
通讯作者:
Cowman, Alan F.
Cowman, Alan F.
中科院分区:
医学2区
文献类型:
--
作者:
Baum, Jake;Chen, Lin;Cowman, Alan F.

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红细胞的侵入是疟原虫生活史的先决条件。网织红细胞结合同源物家族(PfRh)的成员参与了入侵过程,在某些情况下,已被证明是粘附素,与红细胞表面的特异性受体结合。我们已经确定了一个进一步的,puperidine必需的,PfRh家族成员在最致命的人类疟疾恶性疟原虫,称为PfRh 5,它结合到一个未知的类别的糖基化受体的红细胞表面。这种蛋白质是非典型PfRh家族成员,比其他蛋白质小得多,并且在C末端缺乏跨膜和胞质区域。这表明它可能是功能蛋白复合物的一部分。PfRh5定位于裂殖子中的棒状体,并在红细胞侵入过程中遵循紧密连接。此外,针对胞外结构域的一部分产生的兔免疫血清在体外抑制寄生虫入侵。我们假设PfRh5粘附素在红细胞选择和侵袭承诺中起重要作用。考虑到PfRh5的小尺寸,我们相信它可能被证明是一个有价值的候选者,可用于多组分抗疟疾疫苗。(c)2008年澳大利亚寄生虫学会由爱思唯尔有限公司出版。保留所有权利。
Invasion of erythrocytes is a prerequisite in the life history of the malaria parasite. Members of the reticulocyte-binding homologue family (PfRh) have been implicated in the invasion process and in some cases have been shown to act as adhesins, binding to specific receptors on the erythrocyte surface. We have identified a further, putatively essential, PfRh family member in the most virulent human malaria Plosmodium falciparum, called PfRh5, which binds to an unknown class of glycosylated receptors on the erythrocyte surface. This protein is an atypical PfRh family member, being much smaller than others and lacking a transmembrane and cytosolic region at the C-terminus. This suggests it may be part of a functional protein complex. PfRh5 localises to the rhoptries in merozoites and follows the tight junction during the process of erythrocyte invasion. Furthermore, rabbit immune serum raised against a portion of the ecto-domain, inhibits parasite invasion in vitro. We hypothesise an essential role for the PfRh5 adhesin in erythrocyte selection and commitment to invasion. Given its small size, we believe PfRh5 may prove to be a valuable candidate for inclusion in a multi-component anti-malarial vaccine. (c) 2008 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.