Tat and Rev

TAT是一种不同寻常的转录激活剂，通过结合RNA位点(TAR)和 增强病毒LTR的延伸性。TAT和焦油随着细胞的伸长形成更大的复合体 P-TEFb因子，由Cyclin T1(CycT1)和CDK9亚基组成。Tat还与其他蛋白相互作用。 转录机器。P-TEFb存在于细胞内的两个复合体中。在小型复合体(SC)中， 该蛋白由CycT1和CDK9组成，具有活性，可磷酸化RNA的C末端结构域(CTD POL II，导致处理能力增加。在大复合体(LC)中，它由HEXIM1蛋白和 7SK SnRNA除了P-TEFb外，该激酶是不活跃的。TAT可取代7SK SnRNA中的HEXIM1， 招募现在活跃的P-TEFb到HIV LTR。到目前为止，只有富含Tat精氨酸的核磁共振结构 对基序(臂)肽-焦油RNA和精氨酰胺-焦油二元络合物进行了解析。TAT在中国的应用研究 HARC中心旨在确定TAT-P-TEFb-TAR络合物的结构，以及 与TAR和LC结合的最小TAT-CycT1嵌合体。这些结构将与TAT的结构进行比较- 确定结合面和结合构象异同的焦油络合物 为了更好地理解诱导匹配在TAT功能中的假设作用。

Tat is an unusual transcriptional activator that operates by binding to an RNA site (TAR) and enhancing elongation from the viral LTR. Tat and TAR form a larger complex with the cellular elongation factor P-TEFb, composed of cyclin T1 (CycT1) and Cdk9 subunits. Tat also interacts with other proteins of the transcriptional machinery. P-TEFb exists in two complexes in cells. In the small complex (SC), which consists of CycT1 and Cdk9, the kinase is active and phosphorylates the C-terminal domain (CTD) of RNA Pol II, leading to increased processivity. In the large comlex (LC), which consists of the HEXIM1 protein and 7SK snRNA in addition to P-TEFb, the kinase is inactive. Tat can displace HEXIM1 from 7SK snRNA and recruit the now active P-TEFb to the HIV LTR. To date, the NMR structures of only the Tat arginine-rich motif (ARM) peptide-TAR RNA and argininamide-TAR binary complexes have been solved. Studies of Tat in the HARC Center aim to determine the structures of Tat-P-TEFb-TAR complexes, as well as those of a minimal Tat-CycT1 chimera bound to TAR and of the LC. These structures will be compared to those of Tat- TAR complexes to ascertain similarities and differences in the binding surfaces and bound conformations and in order to better understand the postulated roles of induced fit in Tat function.