Sites of interaction between aldolase and thrombospondin-related anonymous protein in Plasmodium
Sites of interaction between aldolase and thrombospondin-related anonymous protein in Plasmodium
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DOI：
10.1091/mbc.e03-06-0355
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发表时间：
2003-12-01
影响因子：
3.3
通讯作者：
Nussenzweig, V
中科院分区：
文献类型：
--
作者：
Buscaglia, CA;Coppens, I;Nussenzweig, V
顶复门寄生虫的滑行运动和宿主细胞入侵是由位于寄生虫质膜下的肌动球蛋白马达赋予的。马达通过属于血小板反应蛋白相关无名蛋白（TRAP）家族的跨膜侵袭素与宿主细胞受体连接。最近的一项研究表明，醛缩酶桥接MIC 2的胞质尾区，弓形虫中的同源TRAP蛋白和肌动蛋白。在这里，我们证实了这些意想不到的发现疟原虫子孢子和确定保守的功能的TRAP家族的胞质尾需要结合醛缩酶：亚末端。色氨酸残基和两个不连续的带负电荷的氨基酸。醛缩酶底物和其他化合物结合到活性位点抑制其与TRAP和与F-肌动蛋白的相互作用，表明马达的功能是代谢调节的。唾液腺子孢子的超微结构研究将醛缩酶定位于含有TRAP的分泌微丝的外周。因此，醛缩酶和TRAP尾之间的相互作用发生在微线的生物发生期间或之前。在与靶细胞接触时，寄生虫前极释放的内容物应同时将醛缩酶、TRAP和可能的F-肌动蛋白带到马达参与的适当亚细胞位置。
Gliding motility and host cell invasion by apicomplexan parasites are empowered by an acto-myosin motor located underneath the parasite plasma membrane. The motor is connected to host cell receptors through trans-membrane invasins belonging to the thrombospondin-related anonymous protein (TRAP) family. A recent study indicates that aldolase bridges the cytoplasmic tail of MIC2, the homologous TRAP protein in Toxoplasma, and actin. Here, we confirm these unexpected findings in Plasmodium sporozoites and identify conserved features of the TRAP family cytoplasmic tail required to bind aldolase: a subterminal. tryptophan residue and two noncontiguous stretches of negatively charged amino acids. The aldolase substrate and other compounds that bind to the active site inhibit its interaction with TRAP and with F-actin, suggesting that the function of the motor is metabolically regulated. Ultrastructural studies in salivary gland sporozoites localize aldolase to the periphery of the secretory micronemes containing TRAP. Thus, the interaction between aldolase and the TRAP tail takes place during or preceding the biogenesis of the micronemes. The release of their contents in the anterior pole of the parasite upon contact with the target cells should bring simultaneously aldolase, TRAP and perhaps F-actin to the proper subcellular location where the motor is engaged.