Structure of the essential Plasmodium host cell traversal protein SPECT1.

Structure of the essential Plasmodium host cell traversal protein SPECT1.
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必需疟原虫宿主细胞遍历蛋白Spect1的结构。

DOI:
10.1371/journal.pone.0114685
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Ghosh P
Ghosh P
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Hamaoka BY;Ghosh P

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疟原虫是导致疟疾的原生动物,它对宿主细胞的遍历是这种寄生虫毒力的重要组成部分。在这个过程中,寄生虫通过寄生虫诱导的毛孔进入宿主细胞,穿过宿主细胞,然后离开宿主细胞。伯氏原虫的子孢子形式需要两种伯氏杆菌蛋白SPECT1和SPECT2来穿越宿主细胞。在两者都没有的情况下,没有观察到气孔的形成。虽然SPECT2与造孔蛋白有序列同源性,但SPECT1与已知结构或功能的蛋白质没有同源性。在这里,我们展示了P.berghei SPECT1略有截断的版本的2.75?分辨率结构。结构显示,蛋白质形成一个四螺旋束,具有一个罕见的特征,即所有这些螺旋平行或反平行排列。同样值得注意的是,在蛋白质中存在一个巨大的、保守的疏水内腔,它可能构成一个配体结合部位,或指示SPECT1的部分不稳定,或两者兼而有之。SPECT1的结构将使有针对性的突变实验成为可能,目的是了解其在宿主细胞穿越中的作用机制。
Host cell traversal by Plasmodium, the protozoan cause of malaria, is an essential part of this parasite's virulence. In this process, the parasite enters a host cell through a parasite-induced pore, traverses the host cell, and then exits the host cell. Two P. berghei proteins, SPECT1 and SPECT2, are required for host cell traversal by the sporozoite form of the parasite. In the absence of either, no pore formation is observed. While SPECT2 has sequence homology to pore-forming proteins, SPECT1 has no homology to proteins of known structure or function. Here we present the 2.75 Å resolution structure of a slightly truncated version of P. berghei SPECT1. The structure reveals that the protein forms a four-helix bundle, with the rare feature of having all of these helices in parallel or antiparallel alignment. Also notable is the presence of a large, conserved, hydrophobic internal cavity in the protein, which may constitute a ligand-binding site or be indicative of partial instability in SPECT1, or both. The structure of SPECT1 will make possible targeted mutagenesis experiments aimed at understanding its mechanism of action in host cell traversal.
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发表时间: 2005-07-01
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