Apolipoprotein E isoform-specific binding to the low-density lipoprotein receptor.
Apolipoprotein E isoform-specific binding to the low-density lipoprotein receptor.
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DOI：
10.1016/j.ab.2007.09.005
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发表时间：
2008-01
影响因子：
2.9
通讯作者：
Taichi Yamamoto;H. Choi;R. Ryan
中科院分区：
文献类型：
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作者：
Taichi Yamamoto;H. Choi;R. Ryan
载脂蛋白E（apoE）是低密度脂蛋白受体（LDLR）家族成员的配体，在血浆胆固醇稳态中发挥作用。基于荧光的测定已被用于受体-配体相互作用的分子研究。竞争实验揭示了脂质相关apoE N末端（NT）结构域与重组可溶性LDLR（sLDLR）结合的异构体特异性差异。以类似的方式，脂质相关的全长apoE 3显示出与sLDLR的结合活性，但不含脂质。分子伴侣，受体相关蛋白，抑制apoE 3-NT-磷脂复合物与sLDLR的结合。apoE 3-NT-磷脂复合物与sLDLR相互作用的动力学研究揭示了apoE-NT亚型与sLDLR结合的时间依赖性效应。结果揭示了一种识别方法，用于研究可能影响受体功能的配体相互作用的分子基础，以维持全身胆固醇稳态。
Apolipoprotein E (apoE) is a ligand for members of the low-density lipoprotein receptor (LDLR) family and functions in plasma cholesterol homeostasis. A fluorescence-based assay has been employed in molecular studies of receptor–ligand interactions. Competition experiments revealed isoform-specific differences in binding of lipid-associated apoE N terminal (NT) domain to a recombinant soluble LDLR (sLDLR). In a similar manner, lipid-associated—but not lipid-free—full-length apoE3 showed binding activity to sLDLR. The molecular chaperone, receptor-associated protein, inhibited apoE3–NT–phospholipid complex binding to sLDLR. Kinetic studies of apoE3–NT–phospholipid complex interaction with sLDLR revealed time-dependent effects of apoE–NT isoform binding to sLDLR. The results reveal a discerning method for study of the molecular basis of ligand interactions that likely influence receptor function in maintenance of whole body cholesterol homeostasis.