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Cell:MRP1蛋白多药抗性的底物识别结构基础

2017-03-25 AlexYang MedSci原创

多药抗性蛋白MRP1是一个ATP结合转运蛋白盒,对许多的抗癌药物都具有抗性,并且在麻醉剂、抗抑郁药、他汀类药物和抗生素和使用和功效中起着重要作用。另外,MRP1还具有调控氧化还原平衡、炎症反应和激素分泌的作用。最近,研究人员利用冷冻电子显微镜探究了牛MRP1蛋白两种构象的分子结构,包括没有任何底物添加的3.5埃载脂蛋白构象和添加了生理性底物的3.3埃复杂载脂蛋白构象,所添加的生理性底物为白三烯C4

多药抗性蛋白MRP1是一个ATP结合转运蛋白盒,对许多的抗癌药物都具有抗性,并且在麻醉剂、抗抑郁药、他汀类药物和抗生素和使用和功效中起着重要作用。另外,MRP1还具有调控氧化还原平衡、炎症反应和激素分泌的作用。

最近,研究人员利用冷冻电子显微镜探究了牛MRP1蛋白两种构象的分子结构,包括没有任何底物添加的3.5埃载脂蛋白构象和添加了生理性底物的3.3埃复杂载脂蛋白构象,所添加的生理性底物为白三烯C4。研究人员发现,这些结构表明了MRP1可以通过形成一个单独的双边结合位点来识别一系列的具有不同化学结构的底物。同时,研究人员观察到了由白三烯C4诱导的MRP1较大的构象变化,这解释了底物结合来起始ATP水解依赖的转运子的方式特点。研究人员指出,通过对MRP1和P-糖蛋白结构的比较,促进了人们对这两个重要分子在化学疗法多药抗性中的一般的和独特的特点的认识。

原始出处:

Zachary Lee Johnson, Jue Chen. Structural Basis of Substrate Recognition by the Multidrug Resistance Protein MRP1. Cell. 9 March 2017. DOI:http://dx.doi.org/1 0.1016/j.cell.2017.01.041

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    2018-01-13 维他命
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    2017-05-19 yige2012
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