Structural basis of dimerization and nucleic acid binding of human DBHS proteins NONO and PSPC1.
Structural basis of dimerization and nucleic acid binding of human DBHS proteins NONO and PSPC1.
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DOI：
10.1093/nar/gkab1216
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发表时间：
2022-01-11
影响因子：
14.9
通讯作者：
Bond CS
中科院分区：
文献类型：
--
作者：
Knott GJ;Chong YS;Passon DM;Liang XH;Deplazes E;Conte MR;Marshall AC;Lee M;Fox AH;Bond CS
果蝇行为/人类剪接(DBHS)蛋白是一个RNA/DNA结合辅因子家族，负责一系列细胞过程。DBHS蛋白包括非POU结构域的八聚体结合蛋白(NONO)和副斑点蛋白组分1(PSPC1)，这两种蛋白能够形成组合二聚体。在这里，我们描述了人类NONO和PSPC1同源二聚体的晶体结构，代表了未表征的DBHS二聚态。这些结构揭示了二聚界面内一组保守的接触和结构可塑性，这为DBHS类似物之间的二聚体选择性提供了理论基础。此外，溶液X射线散射和伴随的生化实验描述了NONO同源二聚体识别协同RNA的机制。核酸结合依赖于RRM1，似乎受到RRM1的取向的影响，受新发现的“β-CLASP”结构的影响。我们的结构揭示了DBHS同质和异质二聚的分子决定因素，并为理解DBHS蛋白质如何合作识别广泛的RNA靶标提供了基础。DBHS蛋白二聚体与核酸的结合涉及每个单体的RRM1和RRM2。虽然同源二聚体中的两个相同的结合位点没有连接，但RRM1结构域的独立重排以适应核酸需要N端β-卡环的解锁。
The Drosophila behaviour/human splicing (DBHS) proteins are a family of RNA/DNA binding cofactors liable for a range of cellular processes. DBHS proteins include the non-POU domain-containing octamer-binding protein (NONO) and paraspeckle protein component 1 (PSPC1), proteins capable of forming combinatorial dimers. Here, we describe the crystal structures of the human NONO and PSPC1 homodimers, representing uncharacterized DBHS dimerization states. The structures reveal a set of conserved contacts and structural plasticity within the dimerization interface that provide a rationale for dimer selectivity between DBHS paralogues. In addition, solution X-ray scattering and accompanying biochemical experiments describe a mechanism of cooperative RNA recognition by the NONO homodimer. Nucleic acid binding is reliant on RRM1, and appears to be affected by the orientation of RRM1, influenced by a newly identified ‘β-clasp’ structure. Our structures shed light on the molecular determinants for DBHS homo- and heterodimerization and provide a basis for understanding how DBHS proteins cooperatively recognize a broad spectrum of RNA targets. Binding of nucleic acids by DBHS protein dimers involves RRM1 and RRM2 of each monomer. Although the two identical binding sites in a homodimer are not linked, independent rearrangement of RRM1 domains to accommodate nucleic acid requires the unfastening of the N-terminal β-clasp.
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DOI：
10.1107/s0907444905036693
发表时间：
2006-01-01
影响因子：
2.2
作者：
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通讯作者：
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影响因子：
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发表时间：
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10.1107/s0907444904016427
发表时间：
2004-12-01
影响因子：
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