Structure of human phosphatidylcholine transfer protein in complex with its ligand
Structure of human phosphatidylcholine transfer protein in complex with its ligand
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DOI：
10.1038/nsb812
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发表时间：
2002-07-01
期刊：
影响因子：
--
通讯作者：
Cohen, DE
中科院分区：
文献类型：
--
作者：
Roderick, SL;Chan, WW;Cohen, DE
磷脂酰胆碱（PtdChos）是真核细胞中最常见的磷脂类。在哺乳动物细胞中，这些不溶性分子通过一种高度特异性的磷脂酰胆碱转移蛋白（PC-TP）在膜之间转移，该蛋白属于疏水配体结合蛋白的类固醇急性调节蛋白相关转移（START）域超家族。人类PC-TP与二亚油基-PtdCho或棕榈酰-亚油基-PtdCho复合物的晶体结构表明，一个有序的PtdCho分子占据了一个位于中心位置的通道。脂质带正电的胆碱头基团在由三个芳香残基形成的笼中参与阳离子- π相互作用。这些结合决定因子和磷酸化决定因子可能通过涉及两亲性c端螺旋和ω -环的构象变化暴露于膜-水界面的脂质头基团。本文提出的结构为理顺PC-TP对PtdCho的特异性提供了基础，并可能确定START蛋白结合疏水配体的共同特征。
Phosphatidylcholines (PtdChos) comprise the most common phospholipid class in eukaryotic cells. In mammalian cells, these insoluble molecules are transferred between membranes by a highly specific phosphatidylcholine transfer protein (PC-TP) belonging to the steroidogenic acute regulatory protein related transfer (START) domain superfamily of hydrophobic ligand-binding proteins. The crystal structures of human PC-TP in complex with dilinoleoyl-PtdCho or palmitoyl-linoleoyl-PtdCho reveal that a single well-ordered PtdCho molecule occupies a centrally located tunnel. The positively charged choline head-group of the lipid engages in cation-pi interactions within a cage formed by the faces of three aromatic residues. These binding determinants and those for the phosphoryl group may be exposed to the lipid headgroup at the membrane-water interface by a conformational change involving the amphipathic C-terminal helix and an Omega-loop. The structures presented here provide a basis for rationalizing the specificity of PC-TP for PtdCho and may identify common features used by START proteins to bind their hydrophobic ligands.