Structural basis of the RNA-binding specificity of human U1A protein
Structural basis of the RNA-binding specificity of human U1A protein
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DOI：
10.1093/emboj/16.18.5764
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发表时间：
1997-09-15
期刊：
影响因子：
11.4
通讯作者：
Varani, G
中科院分区：
文献类型：
--
作者：
Allain, FHT;Howe, PWA;Varani, G
RNP结构域是真核生物中非常常见的蛋白质结构域，参与识别广泛的RNA结构和序列，人类U1A的两种结构与不同的RNA底物形成的复合体揭示了RNP-RNA识别的重要方面，但也提出了关于结合特异性的起源的有趣的问题。结构域的β-折叠为包装芳香族RNA碱基和疏水蛋白质侧链提供了一个广泛的RNA结合平台，然而，单链核苷酸上的官能团和β-折叠表面残基之间的许多相互作用对于具有不同特异性的RNP蛋白质是共同的，因此对分子识别的贡献有限。本文报道的U1A与RNA聚腺苷化抑制元件复合体的精细结构阐明了RNP结构域主要特异性决定因素(可变环)在分子识别中的作用，RNP蛋白质的最可变区域，环3，在定义分子间界面的全局几何形状方面起着至关重要的作用，与RNA磷酸二酯主链的静电相互作用涉及U1A所特有的蛋白质侧链，这对区分可能是重要的。这一分析为RNA-蛋白质识别提供了一幅新的图景，比起DNA-蛋白质识别，它更接近我们目前对蛋白质-蛋白质识别的理解。
The RNP domain is a very common eukaryotic protein domain involved in recognition of a wide range of RNA structures and sequences, Two structures of human U1A in complex with distinct RNA substrates have revealed important aspects of RNP-RNA recognition, but have also raised intriguing questions concerning the origin of binding specificity. The beta-sheet of the domain provides an extensive RNA-binding platform for packing aromatic RNA bases and hydrophobic protein side chains, However, many interactions between functional groups on the single-stranded nucleotides and residues on the beta-sheet surface are potentially common to RNP proteins with diverse specificity and therefore make only limited contribution to molecular discrimination. The refined structure of the U1A complex with the RNA polyadenylation inhibition element reported here clarifies the role of the RNP domain principal specificity determinants (the variable loops) in molecular recognition, The most variable region of RNP proteins, loop 3, plays a crucial role in defining the global geometry of the intermolecular interface, Electrostatic interactions with the RNA phosphodiester backbone involve protein side chains that are unique to U1A and are likely to be important for discrimination. This analysis provides a novel picture of RNA-protein recognition, much closer to our current understanding of protein-protein recognition than that of DNA-protein recognition.