Patra Kailash P, Johnson Jeff R, Cantin Greg T, Yates John R, Vinetz Joseph M
Department of Medicine, George Palade Laboratories, University of California San Diego, CA 92093, USA.
Proteomics. 2008 Jun;8(12):2492-9. doi: 10.1002/pmic.200700727.
Delineation of the complement of proteins comprising the zygote and ookinete, the early developmental stages of Plasmodium within the mosquito midgut, is fundamental to understand initial molecular parasite-vector interactions. The published proteome of Plasmodium falciparum does not include analysis of the zygote/ookinete stages, nor does that of P. berghei include the zygote stage or secreted proteins. P. gallinaceum zygote, ookinete, and ookinete-secreted/released protein samples were prepared and subjected to Multidimensional protein identification technology (MudPIT). Peptides of P. gallinaceum zygote, ookinete, and ookinete-secreted proteins were identified by MS/MS, mapped to ORFs (> 50 amino acids) in the extent P. gallinaceum whole genome sequence, and then matched to homologous ORFs in P. falciparum. A total of 966 P. falciparum ORFs encoding orthologous proteins were identified; just over 40% of these predicted proteins were found to be hypothetical. A majority of putative proteins with predicted secretory signal peptides or transmembrane domains were hypothetical proteins. This analysis provides a more comprehensive view of the hitherto unknown proteome of the early mosquito midgut stages of P. falciparum. The results underpin more robust study of Plasmodium-mosquito midgut interactions, fundamental to the development of novel strategies of blocking malaria transmission.
疟原虫在蚊子中肠内的早期发育阶段包括合子和动合子,明确构成这些阶段的蛋白质互补情况对于理解寄生虫与载体之间最初的分子相互作用至关重要。已发表的恶性疟原虫蛋白质组未包括对合子/动合子阶段的分析,伯氏疟原虫的蛋白质组也未包括合子阶段或分泌蛋白。制备了鸡疟原虫合子、动合子以及动合子分泌/释放的蛋白质样本,并对其进行多维蛋白质鉴定技术(MudPIT)分析。通过串联质谱(MS/MS)鉴定了鸡疟原虫合子、动合子以及动合子分泌蛋白的肽段,将其定位到鸡疟原虫全基因组序列范围内的开放阅读框(>50个氨基酸),然后与恶性疟原虫中的同源开放阅读框进行匹配。总共鉴定出966个编码直系同源蛋白的恶性疟原虫开放阅读框;其中略超过40%的预测蛋白被发现是假设性的。大多数具有预测分泌信号肽或跨膜结构域的推定蛋白都是假设性蛋白。该分析为迄今未知的恶性疟原虫在蚊子中肠早期阶段的蛋白质组提供了更全面的视角。这些结果为更深入地研究疟原虫与蚊子中肠的相互作用奠定了基础,而这对于开发阻断疟疾传播的新策略至关重要。