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Dynamics of RNA binding to the atypical RNA Recognition Motif (RRM2) in the human La protein as determined by TRESI-HDX-MS

机译:由TRESI-HDX-MS测定的人LA蛋白中的RNA与非典型RNA识别基序(RRM2)的动态。

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A typical RRM fold has 2 α-helicies and a 4 stranded β-sheet as shown in Figure 10. The conserved RNA binding surface lies on β1 and β3 strands highlighted in dark pink. Unlike the RRM shown above, hLa-RRM2 has an atypical structure with an extra α-helix (α3) that lies across the RNA binding surface. Our data suggests that the CTD of hLa has 2 distinct RNA binding modes: 1. When it binds to the ssRNA ligand, the α3 helix partially unwinds, possibly as a means of exposing the RNA binding surface on the β3-strand. 2. When it binds HCV RNA, the same helix becomes less solvent accessible and the loop region that follows becomes more structured evident by the large decreases in deuterium uptake. 3. In addition, the unstructured region of the CTD (residues 326-408) engages the HCV RNA more so than the ssRNA. The binding of hLa-CTD to the HCV RNA is similar to that of the binding of a La homolog p65 with telomerase RNA 6. The p65/TER RNA structure has been previously crystalized and the complex is shown below.
机译:典型的RRM折叠具有2α - 螺旋,如图10所示。保守的RNA结合表面在深粉红色中突出显示的β1和β3股。与上面所示的RRM不同,HLA-RRM2具有非典型结构,具有额外的α-螺旋(α3),其位于RNA结合表面上。我们的数据表明,HLA的CTD具有2种不同的RNA结合模式:1。当它结合SSRNA配体时,α3螺旋部分地放亮,可能是暴露在β3股上的RNA结合表面的手段。 2.当它结合HCV RNA时,相同的螺旋变得较低的溶剂可接近,并且随后的环形区域变得更加结构,在氘摄取中的大降低变得更显明显。另外,CTD的非结构化区域(残留物326-408)比SSRNA更多地接合HCV RNA。 HLA-CTD对HCV RNA的结合类似于La同源物P65与端粒酶RNA的结合的结合.P65 / TER RNA结构已经先前结晶,并且该复合物如下所示。

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