Light-independent phospholipid scramblase activity of bacteriorhodopsin from Halobacterium salinarum.
Light-independent phospholipid scramblase activity of bacteriorhodopsin from Halobacterium salinarum.
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来自盐杆菌的细菌紫红质的光依赖性磷脂酶囊泡活性。
DOI：
10.1038/s41598-017-09835-5
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发表时间：
2017-08-25
影响因子：
4.6
通讯作者：
Menon AK
中科院分区：
文献类型：
--
作者：
Verchère A;Ou WL;Ploier B;Morizumi T;Goren MA;Bütikofer P;Ernst OP;Khelashvili G;Menon AK
亚视黄蛋白细菌视紫红质（BR）是一种七螺旋光依赖性质子泵，存在于古菌盐杆菌的紫色膜中。我们现在表明，当重组成大的单层囊泡时，纯化的BR三聚体表现出光依赖性脂质乱序酶活性，从而促进囊泡膜小叶之间磷脂的跨双层交换，速率> 10，000/三聚体/秒。该活性与最近描述的包括牛视紫红质和真菌TMEM 16蛋白的乱序酶的活性相当。特异性试验表明，BR扰乱常见磷脂的荧光类似物，但不运输糖基化二磷酸类异戊二烯脂质。计算机模拟分析表明，BR的跨膜螺旋1和2中膜暴露的极性残基可以通过协调转运磷脂的极性头基来提供脂质易位的分子基础。与这种可能性相一致，广泛的粗粒度的分子动力学模拟的BR三聚体在明确的磷脂膜显示水渗透沿着跨膜螺旋1与极性残基（Y147跨膜螺旋5）在相邻的原聚体的合作。这些结果表明，脂质转运途径可能位于或接近BR三聚体的原体的界面。
The retinylidene protein bacteriorhodopsin (BR) is a heptahelical light-dependent proton pump found in the purple membrane of the archaeon Halobacterium salinarum. We now show that when reconstituted into large unilamellar vesicles, purified BR trimers exhibit light-independent lipid scramblase activity, thereby facilitating transbilayer exchange of phospholipids between the leaflets of the vesicle membrane at a rate >10,000 per trimer per second. This activity is comparable to that of recently described scramblases including bovine rhodopsin and fungal TMEM16 proteins. Specificity tests reveal that BR scrambles fluorescent analogues of common phospholipids but does not transport a glycosylated diphosphate isoprenoid lipid. In silico analyses suggest that membrane-exposed polar residues in transmembrane helices 1 and 2 of BR may provide the molecular basis for lipid translocation by coordinating the polar head-groups of transiting phospholipids. Consistent with this possibility, extensive coarse-grained molecular dynamics simulations of a BR trimer in an explicit phospholipid membrane revealed water penetration along transmembrane helix 1 with the cooperation of a polar residue (Y147 in transmembrane helix 5) in the adjacent protomer. These results suggest that the lipid translocation pathway may lie at or near the interface of the protomers of a BR trimer.
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影响因子：
62.1
作者：
Ernst, Oliver P.;Lodowski, David T.;Elstner, Marcus;Hegemann, Peter;Brown, Leonid S.;Kandori, Hideki
通讯作者：
Kandori, Hideki
影响因子：
5.6
作者：
Lee, Seok-Yong;Letts, James A.;MacKinnon, Roderick
通讯作者：
MacKinnon, Roderick
影响因子：
6.8
作者：
Brunner, Janine D.;Schenck, Stephan;Dutzler, Raimund
通讯作者：
Dutzler, Raimund
影响因子：
15
作者：
Johner, Niklaus;Mondal, Sayan;Khelashvili, George
通讯作者：
Khelashvili, George
影响因子：
2.9
作者：
Chang, QL;Gummadi, SN;Menon, AK
通讯作者：
Menon, AK