恶性疟原虫1型蛋白磷酸酶在功能上可互补酿酒酵母中的glc7突变体。

Plasmodium falciparum protein phosphatase type 1 functionally complements a glc7 mutant in Saccharomyces cerevisiae.

作者信息

Bhattacharyya Mrinal K, Hong Zheng, Kongkasuriyachai Darin, Kumar Nirbhay

机构信息

Johns Hopkins Malaria Research Institute, The W. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA.

出版信息

Int J Parasitol. 2002 Jun;32(6):739-47. doi: 10.1016/s0020-7519(02)00007-3.

DOI:10.1016/s0020-7519(02)00007-3

PMID:12062492

Abstract

We have identified a new homologue of protein phosphatase type 1 from Plasmodium falciparum, designated PfPP1, which shows 83-87% sequence identity with yeast and mammalian PP1s at the amino acid level. The PfPP1 sequence is strikingly different from all other P. falciparum Ser/Thr phosphatases cloned so far. The deduced 304 amino acid sequence revealed the signature sequence of Ser/Thr phosphatase LRGNHE, and two putative protein kinase C and five putative casein kinase II phosphorylation sites. Calyculin A, a potent inhibitor of Ser/Thr phosphatase 1 and 2A showed hyperphosphorylation of a 51kDa protein among other parasite proteins. Okadaic acid on the other hand, was without any effect suggesting that PP1 activity might predominate over PP2A activity in intra-erythrocytic P. falciparum. Complementation studies showed that PfPP1 could rescue low glycogen phenotype of Saccharomyces cerevisiae glc7 (PP1) mutant, strongly suggesting functional interaction of PfPP1 and yeast proteins involved in glycogen metabolism.

摘要

我们已经从恶性疟原虫中鉴定出一种新型1型蛋白磷酸酶的同源物，命名为PfPP1，它在氨基酸水平上与酵母和哺乳动物的PP1具有83-87%的序列同一性。PfPP1序列与迄今为止克隆的所有其他恶性疟原虫丝氨酸/苏氨酸磷酸酶显著不同。推导的304个氨基酸序列揭示了丝氨酸/苏氨酸磷酸酶LRGNHE的特征序列，以及两个假定的蛋白激酶C和五个假定的酪蛋白激酶II磷酸化位点。Calyculin A是一种有效的丝氨酸/苏氨酸磷酸酶1和2A抑制剂，它使一种51kDa蛋白以及其他寄生虫蛋白发生过度磷酸化。另一方面，冈田酸没有任何作用，这表明在红细胞内的恶性疟原虫中，PP1活性可能比PP2A活性占主导。互补研究表明，PfPP1可以挽救酿酒酵母glc7（PP1）突变体的低糖原表型，这强烈表明PfPP1与参与糖原代谢的酵母蛋白存在功能相互作用。