Guanylyl cyclase activity associated with putative bifunctional integral membrane proteins in Plasmodium falciparum
Guanylyl cyclase activity associated with putative bifunctional integral membrane proteins in Plasmodium falciparum
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DOI：
10.1074/jbc.m001021200
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发表时间：
2000-07-21
影响因子：
4.8
通讯作者：
Baker, DA
中科院分区：
文献类型：
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作者：
Carucci, DJ;Witney, AA;Baker, DA
我们在这里报告，鸟苷酸环化酶的活性与两个大的完整的膜蛋白（PfGC α和PfGC β）在人类疟疾寄生虫恶性疟原虫。不寻常的是，这些蛋白质似乎是双功能的;它们的氨基端区域与P型ATP酶有很强的相似性，羧基端区域的序列和结构与G蛋白依赖性腺苷酸环化酶的序列和结构一致，具有两组六个跨膜序列，每个跨膜序列之后是催化结构域然而，在酶促方面重要的并且存在于哺乳动物腺苷酸环化酶的C2结构域中的氨基酸位于恶性疟原虫蛋白的C1结构域中，反之亦然。这些结构域中的某些关键残基更具有鸟苷酸环化酶的特征。与此一致，在大肠杆菌中PfGC β的催化结构域表达后获得鸟苷酸环化酶活性。在恶性疟原虫中，两种基因的表达在生命周期的有性而非无性血液阶段中可检测到，PfGC α定位于配子体的寄生虫/寄生虫空泡膜区域。哺乳动物和寄生虫鸟苷酸环化酶之间鉴定的深刻结构差异表明该信号传导途径的方面可能在机制上不同。
We report here that guanylyl cyclase activity is associated with two large integral membrane proteins (PfGC alpha and PfGC beta) in the human malaria parasite Plasmodium falciparum. Unusually, the proteins appear to be bifunctional; their amino-terminal regions have strong similarity with P-type ATPases, and the sequence and structure of the carboxyl-terminal regions conform to that of G protein-dependent adenylyl cyclases, with two sets of six transmembrane sequences, each followed by a catalytic domain (C1 and C2), However, amino acids that are enzymatically important and present in the C2 domain of mammalian adenylyl cyclases are located in the C1 domain of the P. falciparam proteins and vice versa, In addition, certain key residues in these domains are more characteristic of guanylyl cyclases, Consistent with this, guanylyl cyclase activity was obtained following expression of the catalytic domains of PfGC beta in Escherichia coli, In P. falciparum, expression of both genes was detectable in the sexual but not the asexual blood stages of the life cycle, and PfGC alpha was localized to the parasite/parasitophorous vacuole membrane region of gametocytes, The profound structural differences identified between mammalian and parasite guanylyl cyclases suggest that aspects of this signaling pathway may be mechanistically distinct.