Mechanism of uncoupling protein action.
Mechanism of uncoupling protein action.
复制标题
解偶联蛋白质作用的机制。
DOI：
10.1042/0300-5127:0290803
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发表时间：
2001
影响因子：
3.9
通讯作者：
Jezek,P
中科院分区：
文献类型：
--
作者：
Garlid,KD;Jaburek,M;Jezek,P
解偶联蛋白（UCP）转运机制的两个相互竞争的模型一致认为脂肪酸（FA）是解偶联所必需的，但它们对于转运哪种离子存在分歧。在克林根伯格模型中，UCP 传导质子。在 Garlid 的模型中，UCP 传导阴离子，就像该基因家族的所有成员一样。在后一种模型中，UCP 将阴离子 FA 头基从膜的一侧转运到另一侧，并且通过质子化 FA 跨双层的快速翻转来完成循环。 FA 类似物、长链烷基磺酸盐的头基通过 UCP 易位，但它们不能引起解偶联，因为这些强酸不能在循环的触发器部分被质子化。我们通过十一烷磺酸盐与普萘洛尔的离子对传输克服了这一限制，这导致磺酸盐像 FA 一样跨膜传递质子。在普萘洛尔和十一烷磺酸盐存在的情况下，可以观察到完全 GDP 敏感的解偶联。该结果证实了 UCP 解偶联的机制需要通过 UCP 传输阴离子 FA 头基，并且质子传输通过双层而不是通过 UCP 发生。
Two competing models of uncoupling protein (UCP) transport mechanism agree that fatty acids (FAs) are obligatory for uncoupling, but they disagree about which ion is transported. In Klingenberg's model, UCPs conduct protons. In Garlid's model, UCPs conduct anions, like all members of this gene family. In the latter model, UCP transports the anionic FA head group from one side of the membrane to the other, and the cycle is completed by rapid flip-flop of protonated FAs across the bilayer. The head groups of the FA analogues, long-chain alkylsulphonates, are translocated by UCP, but they cannot induce uncoupling, because these strong acids cannot be protonated for the flip-flop part of the cycle. We have overcome this limitation by ion-pair transport of undecanesulphonate with propranolol, which causes the sulphonate to deliver protons across the membrane as if it were an FA. Full GDP-sensitive uncoupling is seen in the presence of propranolol and undecanesulphonate. This result confirms that the mechanism of UCP uncoupling requires transport of the anionic FA head group by UCP and that the proton transport occurs via the bilayer and not via UCP.