Expression cloning of SR-BI, a CD36-related class B scavenger receptor.
Expression cloning of SR-BI, a CD36-related class B scavenger receptor.
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DOI：
10.1016/s0021-9258(17)31921-x
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发表时间：
1994-08
期刊：
影响因子：
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通讯作者：
S. Acton;Philipp E. Scherer;H. Lodish;M. Krieger
中科院分区：
文献类型：
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作者：
S. Acton;Philipp E. Scherer;H. Lodish;M. Krieger
清道夫受体是介导修饰脂蛋白内吞作用的完整膜蛋白。其中最早被纯化和克隆的是I型和II型巨噬细胞清道夫受体(SR-AI和SR-AII；A类清道夫受体)。随后，细胞表面蛋白CD36被证明能结合氧化型低密度脂蛋白(氧化型低密度脂蛋白)。从中国仓鼠卵巢(CHO)细胞变异体中，我们通过表达克隆了CD36膜蛋白家族新成员SR-BI的cDNA，其预测的509个氨基酸的蛋白质序列与已知的4个家族成员的同源性约为30%。SR-BI和CD36对乙酰化低密度脂蛋白都表现出高亲和力结合，其表观解离常数约为5微克蛋白质/毫升。通过直接结合或竞争分析，CD36和SR-BI的配体结合特性相似，但不相同；两者都能结合修饰蛋白(乙酰化低密度脂蛋白、氧化低密度脂蛋白、马来化牛血清白蛋白)，但不能结合广泛的其他多阴离子(如岩藻素、聚鸟苷、卡拉胶)，这些都是A类受体的配体。因此，SR-BI和CD36定义了第二类清道夫受体，命名为B类。天然低密度脂蛋白既不与A类受体结合，也不与CD36结合，意外地与SR-BI高亲和力结合。对小鼠组织的Northern印迹分析表明，SR-BI在脂肪中大量表达，在肺和肝脏中也有中等水平的表达。此外，在3T3-L1细胞分化为脂肪细胞时，SR-BI mRNA的表达也被诱导。因此，SR-BI表达的组织分布和与配体的结合特性增加了这种细胞表面受体在脂质代谢中发挥重要作用的可能性。
Scavenger receptors are integral membrane proteins that mediate the endocytosis of modified lipoproteins. The first of these to be purified and cloned were the type I and II macrophage scavenger receptors (SR-AI and SR-AII; class A scavenger receptors). Subsequently, the cell surface protein CD36 was shown to bind oxidized low density lipoprotein (oxidized LDL). From a Chinese hamster ovary (CHO) cell variant we have cloned by expression the cDNA for a new member of the CD36 family of membrane proteins, SR-BI, whose predicted protein sequence of 509 amino acids is approximately 30% identical to those of the four previously identified family members. Both SR-BI and CD36 displayed high affinity binding for acetylated LDL with an apparent dissociation constant on the order of approximately 5 micrograms of protein/ml. The ligand binding specificities of CD36 and SR-BI, determined by direct binding or competition assays, were similar, but not identical; both bind modified proteins (acetylated LDL, oxidized LDL, maleylated bovine serum albumin), but not the broad array of other polyanions (e.g. fucoidin, polyguanosinic acid, carrageenan) which are ligands of the class A receptors. Thus, SR-BI and CD36 define a second class of scavenger receptors, designated class B. Native LDL, which does not bind to either class A receptors or CD36, unexpectedly bound with high affinity to SR-BI. Northern blot analysis of murine tissues showed that SR-BI was most abundantly expressed in fat and was present at moderate levels in lung and liver. Furthermore, SR-BI mRNA expression was induced upon differentiation of 3T3-L1 cells into adipocytes. Thus, the tissue distribution of expression and ligand binding properties of SR-BI raise the possibility that this cell surface receptor may play an important role in lipid metabolism.