New insight into the structure and function of Hfq C-terminus.
New insight into the structure and function of Hfq C-terminus.
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DOI：
10.1042/bsr20140128
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发表时间：
2015-04-28
影响因子：
4
通讯作者：
Arluison V
中科院分区：
文献类型：
--
作者：
Fortas E;Piccirilli F;Malabirade A;Militello V;Trépout S;Marco S;Taghbalout A;Arluison V
越来越多的证据表明，RNA代谢成分组装成超分子细胞结构，介导细胞质膜内的功能区隔化。这种细胞区隔化可能在RNA降解和成熟过程中发挥重要作用。这些成分包括Hfq，一种RNA伴侣蛋白，主要通过与几种小调控ncrna （sRNA）的相互作用参与蛋白质合成的转录后控制。大肠杆菌Hfq在结构上分为两个结构域。一个n端结构域，在单个原聚物内折叠成强烈弯曲的β片，组装成典型的环形六聚环。包含约三分之一蛋白质的c端柔性结构域在本质上似乎是非结构化的。Hfq的rna结合功能主要位于其n端核心，而其柔性结构域的功能仍存在争议，且大部分未知。在本研究中，我们证明了hfq - c末端区域（CTR）具有在体外自组装成长淀粉样纤维结构的内在特性。我们发现Hfq在体内膜相关卷曲结构中的正常定位需要这个c端结构域。这一发现首次确定了迄今为止令人困惑的CTR的功能，并在RNA交易中发挥了似是而非的核心作用。我们发现Hfq c端区（CTR）具有自组装成淀粉样原纤维的内在特性。这个区域是Hfq细胞组装成膜相关卷曲结构所必需的。这项工作为这个自然非结构化的Hfq域建立了一个新的功能。
Accumulating evidence indicates that RNA metabolism components assemble into supramolecular cellular structures to mediate functional compartmentalization within the cytoplasmic membrane of the bacterial cell. This cellular compartmentalization could play important roles in the processes of RNA degradation and maturation. These components include Hfq, the RNA chaperone protein, which is involved in the post-transcriptional control of protein synthesis mainly by the virtue of its interactions with several small regulatory ncRNAs (sRNA). The Escherichia coli Hfq is structurally organized into two domains. An N-terminal domain that folds as strongly bent β-sheets within individual protomers to assemble into a typical toroidal hexameric ring. A C-terminal flexible domain that encompasses approximately one-third of the protein seems intrinsically unstructured. RNA-binding function of Hfq mainly lies within its N-terminal core, whereas the function of the flexible domain remains controversial and largely unknown. In the present study, we demonstrate that the Hfq-C-terminal region (CTR) has an intrinsic property to self-assemble into long amyloid-like fibrillar structures in vitro. We show that normal localization of Hfq within membrane-associated coiled structures in vivo requires this C-terminal domain. This finding establishes for the first time a function for the hitherto puzzling CTR, with a plausible central role in RNA transactions. We showed that Hfq C-terminal region (CTR) has an intrinsic property to self-assemble into amyloid-like fibrils. This region is required for cellular assembly of Hfq into membrane-associated coiled structures. The work establishes a new function for this naturally unstructured Hfq domain.