首页> 外文期刊>Journal of Molecular Biology >RNA recognition by the human U1A protein is mediated by a network of local cooperative interactions that create the optimal binding surface.
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RNA recognition by the human U1A protein is mediated by a network of local cooperative interactions that create the optimal binding surface.

机译:人U1A蛋白的RNA识别是由局部合作相互作用网络介导的,该网络可产生最佳结合表面。

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One of the most common structural motifs in RNA-binding proteins is the RNA-binding domain (RBD). These domains share a common alpha/beta sandwich tertiary fold, and are highly conserved, though they bind diverse RNA targets with a wide range of binding affinities. The N-terminal RNA-binding domain (RBD1) of the human U1A protein binds specifically to stem/loop II of the U1 snRNA with sub-nanomolar affinity. Solvent-exposed aromatic residues on the beta-sheet surface are highly conserved among RBD domains; in RBD1, these are Tyr13 and Phe56, with a unique Gln at position 54. Effects of substitutions at these positions were examined using energetic pairwise coupling to describe the communication between these residues in both the free and RNA-bound states of the protein. 15N NMR experiments were used to determine effects of the beta-sheet substitutions on the structural and dynamic properties of this domain. The combination of thermodynamic pairwise coupling and 15N-backbone dynamics provides direct evidence for local cooperative interactions among Y13, Q54, and F56, and a non-conserved loop that directly affect RNA-binding. The results describe how conserved and non-conserved regions of an RBD can communicate with each other to mediate recognition of the RNA. Copyright 1999 Academic Press.
机译:RNA结合蛋白中最常见的结构基序之一是RNA结合域(RBD)。这些结构域共享一个常见的alpha /β夹心三级折叠,并且高度保守,尽管它们以广泛的结合亲和力结合各种RNA靶标。人U1A蛋白的N端RNA结合结构域(RBD1)以亚纳摩尔亲和力特异性结合U1 snRNA的茎/环II。 β-折叠表面上溶剂暴露的芳族残基在RBD结构域之间高度保守。在RBD1中,它们是Tyr13和Phe56,在第54位具有唯一的Gln。使用能量成对偶合检查了这些位置上的取代作用,以描述蛋白质的游离和RNA结合状态下这些残基之间的通讯。 15N NMR实验用于确定β-sheet取代对该结构域的结构和动力学性质的影响。热力学成对偶联和15N骨干动力学的结合为Y13,Q54和F56之间的局部协作相互作用以及直接影响RNA结合的非保守环提供了直接证据。结果描述了RBD的保守区和非保守区如何相互通讯以介导RNA的识别。版权所有1999,学术出版社。

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