Hypervariability within the Rifin, Stevor and Pfmc-2TM superfamilies in Plasmodium falciparum.

Hypervariability within the Rifin, Stevor and Pfmc-2TM superfamilies in Plasmodium falciparum.
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DOI:
10.1093/nar/gkl942
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发表时间:
2006
影响因子:
14.9
通讯作者:
Templeton TJ
Templeton TJ
中科院分区:
生物学2区
文献类型:
--
作者:
Lavazec C;Sanyal S;Templeton TJ

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人疟疾寄生虫恶性疟原虫具有广泛的蛋白质库,基于这些蛋白质内存在Pexel/VTS红细胞运输基序,这些蛋白质被提议运输到红细胞细胞质或表面。该目录包括预测的2个跨膜(2 TM)蛋白的大家族,包括Rifin,Stevor和Pfmc-2 TM超家族,其中每个家族都具有跨旁系同源物和分离株之间的广泛序列多样性区域,该区域局限于感染红细胞上的拟议表面暴露环。在这里,我们表达表位标记的版本的2 TM蛋白在转基因NF 54寄生虫和目前的证据表明,Stevor和Pfmc-2 TM家族出口到红细胞膜,从而支持宿主免疫压力驱动抗原多样性的循环内的假设。对多种恶性疟原虫分离株的检查表明,Stevor和Pfmc-2 TM蛋白内的高变环具有跨越分离株边界的序列多样性。Pfmc-2 TM基因编码在共享深刻的核苷酸同一性的大型扩增基因座内,这反过来突出了在高变环内观察到的分歧。大多数Pexel/VTS蛋白在亚端粒基因组邻域内组织在一起,因此必须存在一种机制来在选择的基因内以及在这些基因内的高度限定的区域内差异地产生序列多样性。
The human malaria parasite, Plasmodium falciparum, possesses a broad repertoire of proteins that are proposed to be trafficked to the erythrocyte cytoplasm or surface, based upon the presence within these proteins of a Pexel/VTS erythrocyte-trafficking motif. This catalog includes large families of predicted 2 transmembrane (2TM) proteins, including the Rifin, Stevor and Pfmc-2TM superfamilies, of which each possesses a region of extensive sequence diversity across paralogs and between isolates that is confined to a proposed surface-exposed loop on the infected erythrocyte. Here we express epitope-tagged versions of the 2TM proteins in transgenic NF54 parasites and present evidence that the Stevor and Pfmc-2TM families are exported to the erythrocyte membrane, thus supporting the hypothesis that host immune pressure drives antigenic diversity within the loop. An examination of multiple P.falciparum isolates demonstrates that the hypervariable loop within Stevor and Pfmc-2TM proteins possesses sequence diversity across isolate boundaries. The Pfmc-2TM genes are encoded within large amplified loci that share profound nucleotide identity, which in turn highlight the divergences observed within the hypervariable loop. The majority of Pexel/VTS proteins are organized together within sub-telomeric genome neighborhoods, and a mechanism must therefore exist to differentially generate sequence diversity within select genes, as well as within highly defined regions within these genes.
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