Splicing factor proline/glutamine‐rich (SFPQ) is an essential RNA‐binding protein that is implicated in many aspects of nuclear function. The structures of SFPQ and two paralogs, non‐POU domain‐containing octamer‐binding protein and paraspeckle component 1, from the Drosophila behavior human splicing protein family have previously been characterized. The unusual arrangement of the four domains, two RNA‐recognition motifs (RRMs), a conserved region termed the NonA/paraspeckle (NOPS) domain and a C‐terminal coiled coil, in the intertwined dimer provides a potentially unique RNA‐binding surface. However, the molecular details of how the four RRMs in the dimeric SFPQ interact with RNA remain to be characterized. Here, a new crystal structure of the dimerization domain of human SFPQ in the C‐centered orthorhombic space group C222₁ with one monomer in the asymmetric unit is presented. Comparison of the new crystal structure with the previously reported structure of SFPQ and analysis of the solution small‐angle X‐scattering data revealed subtle domain movements in the dimerization domain of SFPQ, supporting the concept of multiple conformations of SFPQ in equilibrium in solution. The domain movement of RRM1, in particular, may reflect the complexity of the RNA substrates of SFPQ. Taken together, the crystal and solution structure analyses provide a molecular basis for further investigation into the plasticity of nucleic acid binding by SFPQ in the absence of the structure in complex with its cognate RNA‐binding partners.

中文翻译：

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人SFPQ同二聚体的新晶体结构和小角度X射线散射分析。

剪接因子脯氨酸/谷氨酰胺丰富（SFPQ）是一种必需的RNA结合蛋白，与核功能的许多方面都有牵连。果蝇行为人类剪接蛋白家族的SFPQ和两个旁系同源物（不含POU域的八聚体结合蛋白和旁斑成分1）的结构先前已被鉴定。交错的二聚体中四个域的异常排列，两个RNA识别基序（RRM），一个被称为NonA /副斑点（NOPS）域的保守区和一个C末端盘绕的线圈，提供了潜在的独特RNA结合表面。但是，二聚体SFPQ中的四个RRM如何与RNA相互作用的分子细节仍有待表征。在这里，人SFPQ的二聚化域的新晶体结构在C提出了不对称单元中具有一个单体的中心正交晶体空间群C 222 ₁。将新晶体结构与先前报道的SFPQ结构进行比较，并分析溶液的小角度X散射数据，发现SFPQ的二聚化域中有微妙的畴运动，从而支持了SFPQ在溶液中处于平衡状态的多种构象。RRM1的域运动尤其可能反映了SFPQ RNA底物的复杂性。总之，晶体和溶液结构分析为进一步研究SFPQ核酸结合的可塑性提供了分子基础，而SFPQ在缺乏与其关联的RNA结合伴侣复合的结构的情况下。