Characterization of a differentially expressed protein that shows an unusual localization to intracellular membranes in Leishmania major
Characterization of a differentially expressed protein that shows an unusual localization to intracellular membranes in Leishmania major
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DOI：
10.1042/0264-6021:3560335
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发表时间：
2001-06-01
影响因子：
4.1
通讯作者：
Smith, DF
中科院分区：
文献类型：
--
作者：
Knuepfer, E;Stierhof, YD;Smith, DF
SHERP基因在硕大利什曼原虫的差异调节LmcDNA 16位点内被发现为串联对。SHERP基因产物（在bar mall下的（s）（h）在bar亲水性下的（e）在bar胞质下的（r）在bar内质网相关下的（p）在bar蛋白下的）在其小尺寸（6.2 kDa）、其酸性pI（4.6）和其在感染性非复制性寄生虫阶段的排他性高水平表达（每个细胞约100000拷贝）方面是不寻常的。迄今尚未发现同系物。二级结构的预测表明，SHERP包含一个两亲性的α-螺旋，这可能是参与蛋白质-蛋白质相互作用。在野生型和过表达的寄生虫中，SHERP已经定位于内质网以及线粒体外膜。鉴于不存在N-末端信号序列、跨膜结构域或可检测的翻译后修饰，该亲水性分子可能是细胞内膜的胞质表面上的外周膜蛋白。这种弱的膜缔合已经在细胞分级分离测定中得到证实，其中SHERP在体内交联后从细胞质重新分布到膜部分。SHERP似乎不参与细胞骨架的重排或寄生虫分化过程中细胞器形态的保护。这种新的蛋白质，推测是一种蛋白质复合物的一部分，在感染性寄生虫，营养缺乏和预先适应的哺乳动物宿主的细胞内生存的作用正在调查中。
The SHERP genes are found as a tandem pair within the differentially regulated LmcDNA16 locus of Leishmania major. The SHERP gene product ((s) under bar mall (h) under bar ydrophilic (e) under bar ndoplasmic (r) under bar eticulum-associated (p) under bar rotein) is unusual in its small size (6.2 kDa), its acidic pI (4.6) and its exclusive, high-level expression (approximate to 100000 copies per cell) in infective non-replicative parasite stages. No homologues have been found to date. Secondary-structure predictions suggest that SHERP contains an amphiphilic alpha -helix that is presumably involved in protein-protein interactions. SHERP has been localized to the endoplasmic reticulum as well as to the outer mitochondrial membrane in both wild-type and over-expressing parasites. Given the absence of an N-terminal signal sequence, transmembrane- spanning domains or detectable post-translational modifications, it is likely that this hydrophilic molecule is a peripheral membrane protein on the cytosolic face of intracellular membranes. This weak membrane association has been confirmed in cell-fractionation assays, in which SHERP redistributes from the cytoplasmic to the membrane fraction after in vivo cross-linking. SHERP does not appear to be involved in rearrangements of the cytoskeleton or conservation of organelle morphology during parasite differentiation. The role of this novel protein, presumed to be part of a protein complex, in infective parasites that are nutrient-deficient and pre-adapted for intracellular survival in the mammalian host is under investigation.