A subset of annular lipids is linked to the flippase activity of an ABC transporter

A subset of annular lipids is linked to the flippase activity of an ABC transporter
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DOI:
10.1038/nchem.2172
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发表时间:
2015-03-01
期刊:
影响因子:
21.8
通讯作者:
Robinson, Carol V.
Robinson, Carol V.
中科院分区:
化学1区
文献类型:
--
作者:
Bechara, Cherine;Noell, Anne;Robinson, Carol V.

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脂质是膜的重要组成部分,可能会影响膜蛋白的性质,但膜包埋蛋白复合物周围的脂质的精确组成往往很难辨别。在这里,我们报告说,对于异二聚体ABC转运TmrAB,脱脂的程度可以通过定时暴露于洗涤剂控制。随后,我们表征了与膜蛋白复合物接触提取的内源性脂质的队列,并表明随着长时间的脱脂,中性脂质的数量减少,有利于其带负电荷的对应物。我们发现,脂质A被保留的转运蛋白,其结合的程度在催化循环过程中降低,这意味着脂质A的释放与腺苷三磷酸水解。总之,这些结果使我们能够提出,环状脂质的一个子集是不变的组成,带负电荷的脂质紧密结合TmrAB,并意味着这个出口商在糖脂易位的作用。
Lipids are critical components of membranes that could affect the properties of membrane proteins, yet the precise compositions of lipids surrounding membrane-embedded protein complexes is often difficult to discern. Here we report that, for the heterodimeric ABC transporter TmrAB, the extent of delipidation can be controlled by timed exposure to detergent. We subsequently characterize the cohort of endogenous lipids that are extracted in contact with the membrane protein complex, and show that with prolonged delipidation the number of neutral lipids is reduced in favour of their negatively charged counterparts. We show that lipid A is retained by the transporter and that the extent of its binding decreases during the catalytic cycle, implying that lipid A release is linked to adenosine tri-phosphate hydrolysis. Together, these results enable us to propose that a subset of annular lipids is invariant in composition, with negatively charged lipids binding tightly to TmrAB, and imply a role for this exporter in glycolipid translocation.