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首页> 外文期刊>Journal of Molecular Biology >The Signature of the Five-Stranded vRRM Fold Defined by Functional, Structural and Computational Analysis of the hnRNP L Protein
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The Signature of the Five-Stranded vRRM Fold Defined by Functional, Structural and Computational Analysis of the hnRNP L Protein

机译：由HNRNP L蛋白的功能，结构和计算分析定义的五链VRRM折叠的签名

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摘要

The RNA recognition motif (RRM) is the far most abundant RNA binding domain. In addition to the typical beta(1)alpha 1 beta(2)beta(3)alpha(2)beta(4) fold, various sub-structural elements have been described and reportedly contribute to the high functional versatility of RRMs. The heterogeneous nuclear ribonucleoprotein L (hnRNP L) is a highly abundant protein of 64 kDa comprising four RRM domains. Involved in many aspects of RNA metabolism, hnRNP L specifically binds to RNAs containing CA repeats or CA-rich clusters. However, a comprehensive structural description of hnRNP L including its sub-structural elements is missing. Here, we present the structural characterization of the RRM domains of hnRNP L and demonstrate their function in repressing exon 4 of SLC2A2 By comparison of the sub-structural elements between the two highly similar paralog families of hnRNP L and PTB, we defined signatures underlying interacting C-terminal coils (ICCs), the RRM34 domain interaction and RRMs with a C-terminal fifth beta-strand, a variation we denoted vRRMs. Furthermore, computational analysis revealed new putative ICC-containing RRM families and allowed us to propose an evolutionary scenario explaining the origins of the ICC and fifth beta-strand sub-structural extensions. Our studies provide insights of domain requirements in alternative splicing mediated by hnRNP L and molecular descriptions for the sub-structural elements. In addition, the analysis presented may help to classify other abundant RRM extensions and to predict structure function relationships. (C) 2015 Elsevier Ltd. All rights reserved.
机译：RNA识别基序（RRM）是最丰富的RNA结合结构域。除了典型的β（1）α1β（2）β（2）α（2）α（2）β（4）倍，已经描述了各种亚结构元素，并据说有助于RRM的高功能典型性。异构核核糖核蛋白L（HNRNP L）是64kDa的高度丰富的蛋白质，其包含四个RRM结构域。参与RNA代谢的许多方面，HNRNP L特异性结合含有Ca重复或富含Ca的簇的RNA。然而，缺少包括其亚结构元素的HNRNP L的综合结构描述。在这里，我们介绍了HNRNP L的RRM结构域的结构表征，并通过比较HNRNP L和PTB的两个高度相似的帕洛洛港家族之间的亚结构元素来抑制SLC2A2的外显子4的功能，我们定义了涉及的签名C末端线圈（ICC），RRM34结构域相互作用和具有C末端第五β-股线的RRMS，其表示VRRMS的变异。此外，计算分析揭示了含有新推定的ICC的RRM系列，并允许我们提出一种进化场景，解释ICC和第五β-股亚结构延伸的起源。我们的研究提供了由HNRNP L介导的替代剪接的域要求的见解，以及用于子结构元素的分子描述。此外，所提供的分析可以有助于对其他丰富的RRM扩展进行分类并预测结构功能关系。 （c）2015 Elsevier Ltd.保留所有权利。

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