A protein interaction network of the malaria parasite Plasmodium falciparum
A protein interaction network of the malaria parasite Plasmodium falciparum
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DOI：
10.1038/nature04104
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发表时间：
2005-11-03
期刊：
影响因子：
64.8
通讯作者：
Hughes, RE
中科院分区：
文献类型：
--
作者：
LaCount, DJ;Vignali, M;Hughes, RE
恶性疟原虫引起最严重的疟疾，每年杀死多达270万人（1）。尽管恶性疟原虫具有全球重要性，但其绝大多数蛋白质尚未通过实验表征。在这里，我们确定恶性疟原虫蛋白质-蛋白质的相互作用，使用高通量版本的酵母双杂交测定，避免了在酿酒酵母中表达恶性疟原虫蛋白质的困难。从超过32，000个酵母双杂交筛选恶性疟原虫蛋白片段，我们确定了2，846个独特的相互作用，其中大多数包括至少一个以前未表征的蛋白质。网络连接的信息学分析，编码相互作用片段的基因的共表达，以及特定蛋白质结构域或基因本体论注释的富集（2）被用于鉴定相互作用蛋白质的组，包括涉及染色质修饰，转录，信使RNA稳定性和泛素化的蛋白质，以及涉及宿主细胞入侵的蛋白质。这些数据构成了对这种重要的人类病原体的蛋白质相互作用网络的第一次广泛描述。
Plasmodium falciparum causes the most severe form of malaria and kills up to 2.7 million people annually(1). Despite the global importance of P. falciparum, the vast majority of its proteins have not been characterized experimentally. Here we identify P. falciparum protein - protein interactions using a high-throughput version of the yeast two-hybrid assay that circumvents the difficulties in expressing P. falciparum proteins in Saccharomyces cerevisiae. From more than 32,000 yeast two-hybrid screens with P. falciparum protein fragments, we identified 2,846 unique interactions, most of which include at least one previously uncharacterized protein. Informatic analyses of network connectivity, coexpression of the genes encoding interacting fragments, and enrichment of specific protein domains or Gene Ontology annotations(2) were used to identify groups of interacting proteins, including one implicated in chromatin modification, transcription, messenger RNA stability and ubiquitination, and another implicated in the invasion of host cells. These data constitute the first extensive description of the protein interaction network for this important human pathogen.