Apolipoprotein E isoform-specific binding to the low-density lipoprotein receptor

IF 2.6 4区生物学 Q2 BIOCHEMICAL RESEARCH METHODS Analytical biochemistry Pub Date : 2008-01-15 DOI:10.1016/j.ab.2007.09.005

Taichi Yamamoto, Hyung Won Choi, Robert O. Ryan

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引用次数: 44

Abstract

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.

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载脂蛋白E亚型特异性结合低密度脂蛋白受体

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起作用。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，脂质相关而非无脂质的全长apoE3显示出与sLDLR的结合活性。分子伴侣，受体相关蛋白，抑制apoe3 - nt -磷脂复合物结合sLDLR。apoe3 - nt -磷脂复合物与sLDLR相互作用的动力学研究揭示了apoE-NT异构体与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。

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来源期刊

Analytical biochemistry 生物-分析化学

CiteScore

5.70

自引率

0.00%

发文量

283

审稿时长

44 days

期刊介绍： The journal''s title Analytical Biochemistry: Methods in the Biological Sciences declares its broad scope: methods for the basic biological sciences that include biochemistry, molecular genetics, cell biology, proteomics, immunology, bioinformatics and wherever the frontiers of research take the field. The emphasis is on methods from the strictly analytical to the more preparative that would include novel approaches to protein purification as well as improvements in cell and organ culture. The actual techniques are equally inclusive ranging from aptamers to zymology. The journal has been particularly active in: -Analytical techniques for biological molecules- Aptamer selection and utilization- Biosensors- Chromatography- Cloning, sequencing and mutagenesis- Electrochemical methods- Electrophoresis- Enzyme characterization methods- Immunological approaches- Mass spectrometry of proteins and nucleic acids- Metabolomics- Nano level techniques- Optical spectroscopy in all its forms. The journal is reluctant to include most drug and strictly clinical studies as there are more suitable publication platforms for these types of papers.