The principal mRNA nuclear export factor NXF1:NXT1 forms a symmetric binding platform that facilitates export of retroviral CTE-RNA.

The principal mRNA nuclear export factor NXF1:NXT1 forms a symmetric binding platform that facilitates export of retroviral CTE-RNA.
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DOI:
10.1093/nar/gkv032
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发表时间:
2015-02-18
影响因子:
14.9
通讯作者:
Stewart M
Stewart M
中科院分区:
生物学2区
文献类型:
--
作者:
Aibara S;Katahira J;Valkov E;Stewart M

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NXF1:NXT1复合体(也称为TAP:p15)是一种通用的mRNA核输出因子,从酵母到人类都是保守的。NXF1是由四个结构域(RRM, LRR, NTF2-like和UBA)组成的模块化蛋白。目前还不清楚NXF1:NXT1是如何结合转录本的,也不清楚NXF1结构域是否有更高的组织。我们在这里报告了3.4 Å分辨率的人类NXF1和NXT1的前三个结构域的晶体结构,NXT1在不对称单元中有两个复本,形成了一个亲密的结构域交换二聚体。在该二聚体中,NXF1 LRR和NTF2-like结构域之间的连接物与NXT1相互作用,形成一个2重对称平台,其中rna结合的RRM、LRR和NTF2-like结构域排列在一个面上。除了大量转录本外,NXF1:NXT1还促进了来自简单d型逆转录病毒(如SRV-1)的非剪接逆转录病毒基因组RNA的输出,这些逆转录病毒含有一个组成性转运元件(CTE),这是一个顺式作用的2倍对称RNA茎环基序。互补的结构、生化和细胞技术表明NXF1二聚化形成对称的RNA结合平台:NXT1促进CTE-RNA的识别并促进其核输出。
The NXF1:NXT1 complex (also known as TAP:p15) is a general mRNA nuclear export factor that is conserved from yeast to humans. NXF1 is a modular protein constructed from four domains (RRM, LRR, NTF2-like and UBA domains). It is currently unclear how NXF1:NXT1 binds transcripts and whether there is higher organization of the NXF1 domains. We report here the 3.4 Å resolution crystal structure of the first three domains of human NXF1 together with NXT1 that has two copies of the complex in the asymmetric unit arranged to form an intimate domain-swapped dimer. In this dimer, the linkers between the NXF1 LRR and NTF2-like domains interact with NXT1, generating a 2-fold symmetric platform in which the RNA-binding RRM, LRR and NTF2-like domains are arranged on one face. In addition to bulk transcripts, NXF1:NXT1 also facilitates the export of unspliced retroviral genomic RNA from simple type-D retroviruses such as SRV-1 that contain a constitutive transport element (CTE), a cis-acting 2-fold symmetric RNA stem–loop motif. Complementary structural, biochemical and cellular techniques indicated that the formation of a symmetric RNA binding platform generated by dimerization of NXF1:NXT1 facilitates the recognition of CTE-RNA and promotes its nuclear export.
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发表时间: 2010-02
期刊: Acta crystallographica. Section D, Biological crystallography
影响因子: --
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通讯作者: Zwart PH