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Ras超家族是由一群具有保守氨基酸基序的GTP结合蛋白组成,作为双向分子开关对细胞的多种功能具有调节重要的作用。本文报告分离得到一个新的阴道毛滴虫Ras cDNA克隆,命名为TvRasC。TvRasC cDNA编码一个194氨基酸的蛋白,与其它Ras亚家族成员蛋白序列的一致性在46 %到52 %之间。序列分析表明,该蛋白序列拥有Ras亚家族保守的结合GTP结构域。进化树分析发现该基因与人类的Rit基因位于同一亚群。由于Rit家族成员不含有CAAX异戊烯化基序,而TvRasC在羧基末端有一个典型的CAAX异戊烯化基序,因此TvRasC不属于Rit家族成员。在TvRasC的效应结构域内,与位于HRas第33位的天冬氨酸对应的氨基酸残基是天冬酰胺,有研究表明这种变化将大大削弱Ras基因家族与下游效应分子Raf的结合能力。因此我们预测TvRasC可能只有低水平的GTP酶活性,这种替换有可能使Raf失去与Ras结合域相互作用,并可能导致有活性有丝分裂蛋白激酶没有刺激效应。有关TvRasC在寄生性阴道毛滴虫原虫中的作用有待进一步研究。
The Ras superfamily consists of a group of GTP-binding proteins with conserved amino acid motifs that act as bidirectional molecular switches and play an important regulatory role in many cellular functions. This article reports the isolation of a new Trichomonas vaginalis Ras cDNA clone, named TvRasC. The TvRasC cDNA encodes a 194 amino acid protein that is 46% to 52% identical to other Ras subfamily members. Sequence analysis showed that this protein sequence has a conserved binding to the GTP domain of the Ras subfamily. Phylogenetic tree analysis revealed that the gene is located in the same subgroup as the human Rit gene. TvRasC is not a member of the Rit family because the Rit family members do not contain CAAX prenylation motifs and TvRasC has a typical CAAX prenylation motif at the carboxy terminus. In the effector domain of TvRasC, the amino acid residue corresponding to aspartic acid located at position 33 of HRas is asparagine. Studies have shown that this change will greatly impair the ability of the Ras gene family to bind to downstream effector Raf. Therefore, we predict that TvRasC may have only low levels of GTPase activity. This substitution may result in loss of Raf interaction with the Ras-binding domain and may result in no stimulatory effect of the active mitotic protein kinase. The role of TvRasC in parasitic Trichomonas vaginalis remains to be further studied.