The structure of the mRNA export factor TAP reveals a cis arrangement of a non-canonical RNP domain and an LRR domain
The structure of the mRNA export factor TAP reveals a cis arrangement of a non-canonical RNP domain and an LRR domain
复制标题
DOI：
10.1093/emboj/19.21.5587
复制
发表时间：
2000-11-01
期刊：
影响因子：
11.4
通讯作者：
Conti, E
中科院分区：
文献类型：
--
作者：
Liker, E;Fernandez, E;Conti, E
人类 TAP 参与 mRNA 核输出，并被猿猴 D 型逆转录病毒用来将其未剪接的基因组 RNA 输出到宿主细胞的细胞质。我们已经确定了结合逆转录病毒RNA组成型转运元件（CTE）的最小TAP片段的晶体结构，出乎意料的是，我们发现该片段由一个无法通过其序列识别的核糖核蛋白（RNP）结构域和一个富含亮氨酸的重复（LRR）结构域组成。非规范 RNP 结构域充当片段的一般 RNA 结合部分。 LRR 结构域需要与 RNP 结构域顺式才能结合 CTE RNA。这些结构域的结构和生化特性表明与 U2B"(RNP)-UZA'(LRR) 剪接体异二聚体显着相似。我们使用基于结构的突变体进行的体外和体内功能研究表明，TAP LRR 结构域的系统发育保守表面可能在病毒和细胞 RNA 的输出中发挥不同的作用。
Human TAP is implicated in mRNA nuclear export and is used by simian type D retroviruses to export their unspliced genomic RNA to the cytoplasm of the host cell. We have determined the crystal structure of the minimal TAP fragment that binds the constitutive transport element (CTE) of retroviral RNAs, Unexpectedly, we find the fragment consists of a ribonucleoprotein (RNP) domain, which is not identifiable by its sequence, and a leucine-rich repeat (LRR) domain. The non-canonical RNP domain functions as the general RNA-binding portion of the fragment. The LRR domain is required lit cis to the RNP domain for CTE RNA binding. The structural and biochemical properties of the domains point to a remarkable similarity with the U2B"(RNP)-UZA'(LRR) spliceosomal heterodimer. Our in vitro and in vivo functional studies using structure-based mutants suggest that a phylogenetically conserved surface of the LRR domain of TAP may have different roles in the export of viral and cellular RNAs.