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首页> 外文期刊>Biochemistry >Differential Binding of Ligands to the Apolipoprotein E Receptor 2
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Differential Binding of Ligands to the Apolipoprotein E Receptor 2

机译：配体与载脂蛋白E受体2的差异结合。

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Apolipoprotein E receptor 2(apoER2) is an important participant in the Reelin signaling pathway that directs cell positioning during embryogenesis, ApoER2 is a cell surface molecule that elicits intracellular signal transduction through binding of Reelin. The structural requirements for Reelin binding to apoER2 and the receptor domains involved in this process are unclear at present. Using a series of receptor mutants, we characterized the interaction of apoERA2 with Reelin and compared this interaction to that of apoER2 with the receptor-associated protein (RAP), an apoER2 ligand that does not induce signaling. By surface plasmon resonance we demonstrate that apoER2 exhibits 6-fold higher affinity for Reelin than the very low density lipoprotein receptor (VLDLR), which also functions as a Reelin receptor (K_D 0.2 Nm versus K_D 1.2 Nm). Acidic amino acid residues in complement-type repeat domains 1 and 3 of apoER2 are required for Reelin binding. The same regions of the receptor are also bound by RAP with a 25-fold lower affinity (K_d 5 nM). Whereas RAP binds to apoER2 with a 1:1 stoichiometry, experimental evidence suggests that Reelin associates with two or more receptor molecules simultaneously to achieve highaffinity interaction. This finding indicates that aggregation of apoER2 by multivalent ligands such as Reelin may be the structural basis for signal transduction.
机译：载脂蛋白E受体2（apoER2）是Reelin信号通路中重要的参与者，该信号通路指导胚胎发生过程中的细胞定位。ApoER2是一种细胞表面分子，通过Reelin的结合引发细胞内信号转导。目前尚不清楚Reelin与apoER2结合的结构要求和参与该过程的受体结构域。使用一系列受体突变体，我们表征了apoERA2与Reelin的相互作用，并将这种相互作用与apoER2与受体相关蛋白（RAP）（一种不诱导信号传导的apoER2配体）的相互作用进行了比较。通过表面等离子体共振，我们证明apoER2对Reelin的亲和力比非常低密度的脂蛋白受体（VLDLR）高6倍，后者也起Reelin受体的作用（K_D 0.2 Nm对K_D 1.2 Nm）。 Reelin结合需要apoER2的补体型重复域1和3中的酸性氨基酸残基。受体的相同区域也被RAP结合，亲和力降低了25倍（K_d 5 nM）。尽管RAP以1：1的化学计量比与apoER2结合，但实验证据表明Reelin同时与两个或多个受体分子缔合以实现高亲和力相互作用。该发现表明，多价配体例如Reelin对apoER2的聚集可能是信号转导的结构基础。

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