Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
Nat Struct Mol Biol. 2011 Aug 7;18(9):990-8. doi: 10.1038/nsmb.2094.
mRNA export is mediated by the TAP-p15 heterodimer, which belongs to the family of NTF2-like export receptors. TAP-p15 heterodimers also bind to the constitutive transport element (CTE) present in simian type D retroviral RNAs, and they mediate the export of viral unspliced RNAs to the host cytoplasm. We have solved the crystal structure of the RNA recognition and leucine-rich repeat motifs of TAP bound to one symmetrical half of the CTE RNA. L-shaped conformations of protein and RNA are involved in a mutual molecular embrace on complex formation. We have monitored the impact of structure-guided mutations on binding affinities in vitro and transport assays in vivo. Our studies define the principles by which CTE RNA subverts the mRNA export receptor TAP, thereby facilitating the nuclear export of viral genomic RNAs, and, more generally, provide insights on cargo RNA recognition by mRNA export receptors.
mRNA 输出由 TAP-p15 异二聚体介导，该异二聚体属于 NTF2 样输出受体家族。TAP-p15 异二聚体还与猴 D 型逆转录病毒 RNA 中存在的组成型转运元件 (CTE) 结合，并介导病毒未剪接 RNA 向宿主细胞质的输出。我们已经解决了与 CTE RNA 对称半部分结合的 TAP 的 RNA 识别和亮氨酸丰富重复基序的晶体结构。在复合物形成过程中，蛋白质和 RNA 的 L 形构象涉及相互分子拥抱。我们监测了结构指导突变对体外结合亲和力和体内运输测定的影响。我们的研究定义了 CTE RNA 颠覆 mRNA 输出受体 TAP 的原则，从而促进病毒基因组 RNA 的核输出，更普遍地为 mRNA 输出受体对货物 RNA 的识别提供了见解。
