The two sides of a lipid-protein story.
The two sides of a lipid-protein story.
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DOI：
10.1007/s12551-016-0199-5
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发表时间：
2016-06-01
影响因子：
--
通讯作者：
Costa-Filho, Antonio J
中科院分区：
文献类型：
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作者：
Basso, Luis G Mansor;Mendes, Luis F Santos;Costa-Filho, Antonio J
蛋白质-膜相互作用在多种细胞功能中发挥着重要作用，如信号传递、膜运输和运输。膜募集的胞浆蛋白与脂质双层瞬时和界面相互作用，执行其中的几项功能。能够探测这种弱关联的结构动力学变化的实验技术令人惊讶地有限。在这些技术中，电子自旋共振(ESR)具有巨大的优势，通过在金属蛋白中使用固有的顺磁探针或通过将氮氧化物自旋标记附着在蛋白质和脂类上，从膜和蛋白质的角度提供有价值的局部信息。在这篇综述中，我们讨论了ESR揭示脂质-外周膜蛋白相互作用的相关结构和功能细节的能力，特别是蛋白质和/或脂类特定区域的局部变化。首先，我们展示了如何使用ESR来研究蛋白质和特定脂类之间的直接相互作用，说明了脂类结合到氯代邻苯二酚1，2-双加氧酶的疏水口袋中的情况，氯代邻苯二酚1，2-双加氧酶是一种非血红素铁酶，负责在环境中工业释放的芳香化合物的分解代谢。在第二个案例中，我们展示了GPI锚定的组织非特异性碱性磷酸酶，一种在骨骼矿化中起关键作用的蛋白质，以及对脂酰链的有序性和动力学的影响。然后，转到蛋白质的角度，我们分析了脑脂肪酸结合蛋白与模型膜的相互作用，脑脂肪酸结合蛋白是长链、饱和或不饱和脂肪酸等疏水配体可逆结合和运输的主要参与者。最后，我们讨论了如何将脂质和蛋白质观点联系起来，以解决一个共同的问题，即二氢罗酸脱氢酶的分子机制，以及它是如何从膜上捞出包埋在膜上的苯二酚来执行其功能的。二氢罗酸脱氢酶是从头合成嘧啶核苷酸的关键酶。
Protein-membrane interactions play essential roles in a variety of cell functions such as signaling, membrane trafficking, and transport. Membrane-recruited cytosolic proteins that interact transiently and interfacially with lipid bilayers perform several of those functions. Experimental techniques capable of probing changes on the structural dynamics of this weak association are surprisingly limited. Among such techniques, electron spin resonance (ESR) has the enormous advantage of providing valuable local information from both membrane and protein perspectives by using intrinsic paramagnetic probes in metalloproteins or by attaching nitroxide spin labels to proteins and lipids. In this review, we discuss the power of ESR to unravel relevant structural and functional details of lipid-peripheral membrane protein interactions with special emphasis on local changes of specific regions of the protein and/or the lipids. First, we show how ESR can be used to investigate the direct interaction between a protein and a particular lipid, illustrating the case of lipid binding into a hydrophobic pocket of chlorocatechol 1,2-dioxygenase, a non-heme iron enzyme responsible for catabolism of aromatic compounds that are industrially released in the environment. In the second case, we show the effects of GPI-anchored tissue-nonspecific alkaline phosphatase, a protein that plays a crucial role in skeletal mineralization, and on the ordering and dynamics of lipid acyl chains. Then, switching to the protein perspective, we analyze the interaction with model membranes of the brain fatty acid binding protein, the major actor in the reversible binding and transport of hydrophobic ligands such as long-chain, saturated, or unsaturated fatty acids. Finally, we conclude by discussing how both lipid and protein views can be associated to address a common question regarding the molecular mechanism by which dihydroorotate dehydrogenase, an essential enzyme for the de novo synthesis of pyrimidine nucleotides, and how it fishes out membrane-embedded quinones to perform its function.