A new crystal structure and small-angle X-ray scattering analysis of the homodimer of human SFPQ
A new crystal structure and small-angle X-ray scattering analysis of the homodimer of human SFPQ
复制标题
DOI：
10.1107/s2053230x19006599
复制
发表时间：
2019-06-01
影响因子：
0.9
通讯作者：
Lee, Mihwa
中科院分区：
文献类型：
--
作者：
Hewage, Thushara Welwelwela;Caria, Sofia;Lee, Mihwa
剪接因子脯氨酸/谷氨酰胺丰富（SFPQ）是一种重要的RNA结合蛋白，涉及核功能的许多方面。SFPQ和两个旁系同源物，非POU结构域的八聚体结合蛋白和paraspeckle组件1，从果蝇的行为人类剪接蛋白家族的结构已被表征。四个结构域，两个RNA识别基序（RRM），一个保守的区域称为NonA/paraspeckle（NOPS）结构域和一个C-末端卷曲螺旋的不寻常的安排，在交织的二聚体提供了一个潜在的独特的RNA结合表面。然而，在二聚体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，一个新的晶体结构的二聚化域的人SFPQ在C-中心正交空间群C2221与一个单体的不对称单元。新的晶体结构与先前报道的结构的SFPQ和分析的解决方案的小角度X-散射数据的比较显示微妙的域运动在二聚域的SFPQ，支持的概念，在平衡的SFPQ在溶液中的多个构象。RRM 1的结构域移动，特别是，可能反映了SFPQ的RNA底物的复杂性。两者合计，晶体和溶液结构分析提供了进一步调查的可塑性的核酸结合SFPQ在没有复杂的结构与其同源RNA结合的合作伙伴的分子基础。
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.