How to move an amphipathic molecule across a lipid bilayer: different mechanisms for different ABC transporters?
How to move an amphipathic molecule across a lipid bilayer: different mechanisms for different ABC transporters?
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DOI：
10.1042/bst20160040
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发表时间：
2016-06-15
影响因子：
3.9
通讯作者：
Baker A
中科院分区：
文献类型：
--
作者：
Theodoulou FL;Carrier DJ;Schaedler TA;Baldwin SA;Baker A
β-氧化底物进入过氧化物酶体是由属于亚家族D的ATP结合盒（ABC）转运蛋白介导的。为了进入β-氧化途径，脂肪酸通过转化为脂肪酰辅酶A酯来活化，该反应由酰基辅酶A合成酶（ACS）催化。在这里，我们提出了一个不寻常的运输机制，其中脂肪酰辅酶A底物接受ABC亚类D蛋白（ABCD）的转运蛋白，裂解的转运蛋白在运输过程中跨越脂质双层释放辅酶A，并最终重新酯化的过氧化物酶体腔中的ACS与转运蛋白相互作用的证据。我们建议，这解决了生物物理问题的移动两亲分子的过氧化物酶体膜，因为固有的硫酯酶活性的转运允许单独的膜易位途径的疏水性脂肪酸部分和极性CoA部分。当与不同的过氧化物酶体ACS结合时，裂解/再酯化机制也有可能控制不同底物进入β-氧化途径。两亲分子穿过脂质双层的运动的不同解决方案由细菌脂质连接寡糖（LLO）翻转酶PglK部署，其中基质的亲水性头部基团和疏水性聚异戊二烯尾部被提出具有不同的易位途径，但在运输期间不被化学分离。我们讨论了ABCD蛋白的一个推测性的交替访问模型的基础上与抗原处理（TAP）的哺乳动物ABC转运蛋白，并将其与最近的PglK晶体结构和生化数据所提出的新机制进行比较。
Import of β-oxidation substrates into peroxisomes is mediated by ATP binding cassette (ABC) transporters belonging to subfamily D. In order to enter the β-oxidation pathway, fatty acids are activated by conversion to fatty acyl-CoA esters, a reaction which is catalysed by acyl-CoA synthetases (ACSs). Here, we present evidence for an unusual transport mechanism, in which fatty acyl-CoA substrates are accepted by ABC subclass D protein (ABCD) transporters, cleaved by the transporters during transit across the lipid bilayer to release CoA, and ultimately re-esterified in the peroxisome lumen by ACSs which interact with the transporter. We propose that this solves the biophysical problem of moving an amphipathic molecule across the peroxisomal membrane, since the intrinsic thioesterase activity of the transporter permits separate membrane translocation pathways for the hydrophobic fatty acid moiety and the polar CoA moiety. The cleavage/re-esterification mechanism also has the potential to control entry of disparate substrates into the β-oxidation pathway when coupled with distinct peroxisomal ACSs. A different solution to the movement of amphipathic molecules across a lipid bilayer is deployed by the bacterial lipid-linked oligosaccharide (LLO) flippase, PglK, in which the hydrophilic head group and the hydrophobic polyprenyl tail of the substrate are proposed to have distinct translocation pathways but are not chemically separated during transport. We discuss a speculative alternating access model for ABCD proteins based on the mammalian ABC transporter associated with antigen processing (TAP) and compare it to the novel mechanism suggested by the recent PglK crystal structures and biochemical data.