Structure of an LDLR-RAP complex reveals a general mode for ligand recognition by lipoprotein receptors
Structure of an LDLR-RAP complex reveals a general mode for ligand recognition by lipoprotein receptors
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DOI：
10.1016/j.molcel.2006.02.021
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发表时间：
2006-04-21
期刊：
影响因子：
16
通讯作者：
Blacklow, SC
中科院分区：
文献类型：
--
作者：
Fisher, C;Beglova, N;Blacklow, SC
低密度脂蛋白受体（LDLR）家族的蛋白质在其结合极其多样的蛋白质和脂蛋白配体的能力方面是显著的，但是对配体识别的基础知之甚少。在这里，我们报告了1.26（A）在圆X射线结构的复合物之间的两个模块的区域的配体结合结构域的LDLR和RAP的第三个域，一个护送蛋白的LDLR家族成员。RAP结构域形成具有两个对接位点的三螺旋束，每个对接位点用于每个LDLR模块。每个位点的识别模式几乎相同：来自每个LDLR模块的三个保守的钙配位酸性残基环绕从RAP的第二螺旋突出的赖氨酸侧链。这种金属依赖性静电识别模式，以及使用多个位点产生的亲合力效应，代表了可能适用于其他碱性配体与LDLR家族蛋白结合的一般结合策略。
Proteins of the low-density lipoprotein receptor (LDLR) family are remarkable in their ability to bind an extremely diverse range of protein and lipoprotein ligands, yet the basis for ligand recognition is poorly understood. Here, we report the 1.26 (A) over circle X-ray structure of a complex between a two-module region of the ligand binding domain of the LDLR and the third domain of RAP, an escort protein for LDLR family members. The RAP domain forms a three-helix bundle with two docking sites, one for each LDLR module. The mode of recognition at each site is virtually identical: three conserved, calcium-coordinating acidic residues from each LDLR module encircle a lysine side chain protruding from the second helix of RAP. This metal-dependent mode of electrostatic recognition, together with avidity effects resulting from the use of multiple sites, represents a general binding strategy likely to apply in the binding of other basic ligands to LDLR family proteins.