Schmid Aline, Sauvage Virginie, Escotte-Binet Sandie, Aubert Dominique, Terryn Christine, Garnotel Roselyne, Villena Isabelle
Laboratoire de Parasitologie-Mycologie, EA 3800, IFR 53, UFR Médecine, Université de Reims Champagne-Ardenne, 51 rue Cognacq-Jay, 51095 Reims cedex, France.
Mol Biochem Parasitol. 2009 Jan;163(1):54-60. doi: 10.1016/j.molbiopara.2008.09.010. Epub 2008 Oct 17.
ATP-binding cassette (ABC) transporters represent an important family of membrane proteins involved in drug resistance and other biological activities. The present study reports on the characterization of a P-glycoprotein (Pgp), TgABC.B1, in the protozoan parasite Toxoplasma gondii. The protein encoded by the TgABC.B1 gene displays the typical (TMD-NBD)2 structural organization of the "full" ABC transporter and shows significant identity and similarity with two apicomplexan Pgps; Pgh1 in Plasmodium falciparum and CpABC3 in Cryptosporidium parvum. The TgABC.B1 gene is a single copy gene transcribed into a full-length mRNA of 4.3kb and expressed as a protein of approximately 150kDa, which cellular localization revealed a membrane-associated labelling in tachyzoites. The TgABC.B1 gene is constitutively expressed in the three major T. gondii genotypes but demonstrated a higher expression in virulent type I, at both transcriptional and translational levels. Further characterization of this Pgp-like protein will increase our knowledge of the membrane transport system in this parasite and could result in the identification of a new therapeutic target in Toxoplasma.
ATP结合盒（ABC）转运蛋白是参与耐药性及其他生物学活性的一类重要膜蛋白。本研究报告了原生动物寄生虫刚地弓形虫中一种P-糖蛋白（Pgp）TgABC.B1的特性。TgABC.B1基因编码的蛋白质呈现出“完整”ABC转运蛋白典型的（跨膜结构域-核苷酸结合结构域）2结构组织，并且与两种顶复门Pgp具有显著的同一性和相似性，即恶性疟原虫中的Pgh1和微小隐孢子虫中的CpABC3。TgABC.B1基因是单拷贝基因，转录成4.3kb的全长mRNA，并表达为约150kDa的蛋白质，其细胞定位显示速殖子中有膜相关标记。TgABC.B1基因在刚地弓形虫的三种主要基因型中组成性表达，但在毒力较强的I型中，在转录和翻译水平上均表现出更高的表达。对这种类Pgp蛋白的进一步特性分析将增加我们对该寄生虫膜转运系统的了解，并可能有助于鉴定弓形虫新的治疗靶点。
