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成纤维细胞低密度脂蛋白受体的功能单位:一种具有多个结合位点的100,000道尔顿结构。

Functional unit of the low density lipoprotein receptor of fibroblasts: a 100,000-dalton structure with multiple binding sites.

作者信息

Innerarity T L, Kempner E S, Hui D Y, Mahley R W

出版信息

Proc Natl Acad Sci U S A. 1981 Jul;78(7):4378-82. doi: 10.1073/pnas.78.7.4378.

DOI:10.1073/pnas.78.7.4378
PMID:6270675
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC319793/
Abstract

The low density lipoprotein (apoprotein B,E) receptors of fibroblasts bind plasma lipoproteins that contain either the B (apo-B) or E (apo-E) apoproteins. These include the low density lipoproteins (LDL) containing apo-B and certain high density lipoproteins containing apo-E (e.g., the cholesterol-induced apo-E HDLc). The same receptor binds both LDL and apo-E HDLc, but the apo-E HDLc bind with much higher affinity. This higher affinity is due to the binding of apo-E HDLc to multiple receptor sites. One possible structural model for this receptor is that each apo-B,E receptor possesses a single binding site. Thus, the multiple binding of apo-E HDLc would require the recruitment of four independent receptors to bind to a single apo-E HDLc particle. A second model is that each receptor unit possesses multiple binding sites capable of binding one apo-E HDLc particle or four LDL particles. This study characterizes the apo-B,E receptors in situ in the membranes of fibroblasts by radiation inactivation. This technique allows one to determine the functional size of the receptor on the basis of the amount of radiation required to inactivate the structure. The larger the molecular size of the structure, the less ionizing radiation (generated by a linear accelerator) that will be required to abolish the receptor--ligand interaction. The functional size of the apo-B,E receptor is 106,000 Mr as determined with both LDL and apo-E HDLc binding after radiation inactivation. Furthermore, the data derived from radiation inactivation and Scatchard analysis indicate that each apo-B,E receptor has multiple binding sites and that each functional receptor unit, capable of binding one apo-E HDLc or four LDL particles, has a molecular weight of 106,000.

摘要

成纤维细胞的低密度脂蛋白(载脂蛋白B、E)受体可结合含有B(载脂蛋白B)或E(载脂蛋白E)载脂蛋白的血浆脂蛋白。这些脂蛋白包括含载脂蛋白B的低密度脂蛋白(LDL)和某些含载脂蛋白E的高密度脂蛋白(如胆固醇诱导的载脂蛋白E HDLc)。同一受体可结合LDL和载脂蛋白E HDLc,但载脂蛋白E HDLc的结合亲和力更高。这种更高的亲和力是由于载脂蛋白E HDLc与多个受体位点结合所致。该受体的一种可能结构模型是,每个载脂蛋白B、E受体具有一个单一结合位点。因此,载脂蛋白E HDLc的多重结合需要募集四个独立受体才能与单个载脂蛋白E HDLc颗粒结合。第二种模型是,每个受体单元具有多个结合位点,能够结合一个载脂蛋白E HDLc颗粒或四个LDL颗粒。本研究通过辐射失活对成纤维细胞膜中的载脂蛋白B、E受体进行原位表征。该技术使人们能够根据使结构失活所需的辐射量来确定受体的功能大小。结构的分子尺寸越大,消除受体 - 配体相互作用所需的电离辐射(由直线加速器产生)就越少。辐射失活后,通过LDL和载脂蛋白E HDLc结合测定,载脂蛋白B、E受体的功能大小为106,000道尔顿。此外,来自辐射失活和Scatchard分析的数据表明,每个载脂蛋白B、E受体具有多个结合位点,并且每个能够结合一个载脂蛋白E HDLc或四个LDL颗粒的功能性受体单元的分子量为106,000。

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Cell surface receptor binding of phospholipid . protein complexes containing different ratios of receptor-active and -inactive E apoprotein.含有不同比例受体活性和非活性E载脂蛋白的磷脂-蛋白质复合物的细胞表面受体结合
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