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The structure-function relationship of a signaling-competent, dimeric Reelin fragment
Structure ( IF 4.4 ) Pub Date : 2021-06-04 , DOI: 10.1016/j.str.2021.05.012
Liam S Turk 1 , Xuyuan Kuang 2 , Valentina Dal Pozzo 3 , Khush Patel 3 , Muyuan Chen 4 , Kevin Huynh 5 , Michael J Currie 6 , Daniel Mitchell 7 , Renwick C J Dobson 8 , Gabriella D'Arcangelo 3 , Wei Dai 5 , Davide Comoletti 1
Affiliation  

Reelin operates through canonical and non-canonical pathways that mediate several aspects of brain development and function. Reelin's dimeric central fragment (CF), generated through proteolytic cleavage, is required for the lipoprotein-receptor-dependent canonical pathway activation. Here, we analyze the signaling properties of a variety of Reelin fragments and measure the differential binding affinities of monomeric and dimeric CF fragments to lipoprotein receptors to investigate the mode of canonical signal activation. We also present the cryoelectron tomography-solved dimeric structure of Reelin CF and support it using several other biophysical techniques. Our findings suggest that Reelin CF forms a covalent parallel dimer with some degree of flexibility between the two protein chains. As a result of this conformation, Reelin binds to lipoprotein receptors in a manner inaccessible to its monomeric form and is capable of stimulating canonical pathway signaling.



中文翻译:

具有信号传导能力的二聚体 Reelin 片段的结构-功能关系

Reelin 通过规范和非规范途径运作,这些途径介导大脑发育和功能的几个方面。Reelin 的二聚中心片段 (CF),通过蛋白水解切割产生,是脂蛋白受体依赖性经典途径激活所必需的。在这里,我们分析了各种 Reelin 片段的信号传导特性,并测量了单体和二聚体 CF 片段对脂蛋白受体的不同结合亲和力,以研究典型信号激活的模式。我们还展示了 Reelin CF 的冷冻电子断层扫描解决的二聚体结构,并使用其他几种生物物理技术支持它。我们的研究结果表明,Reelin CF 形成共价平行二聚体,在两条蛋白质链之间具有一定程度的灵活性。由于这种构象,

更新日期:2021-06-04
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