Tat and Rev

达特是一种不寻常的转录激活因子，其通过与RNA位点（TAR）结合而起作用， 增强从病毒LTR的延伸。达特和TAR随着细胞的伸长形成更大的复合物 因子P-TEFb由细胞周期蛋白T1（CycT 1）和Cdk 9亚基组成。达特还与其他蛋白质相互作用， 转录机制P-TEFb在细胞中以两种复合物存在。在小型综合体（SC）中， 由CycT 1和Cdk 9组成，该激酶具有活性并磷酸化RNA的C末端结构域（CTD Pol II，导致持续合成能力增加。在由HEXIM 1蛋白和HEXIM 2蛋白组成的大复合物（LC）中， 除了P-TEFb之外，7SK snRNA激酶是无活性的。达特可以从7SK snRNA置换HEXIM 1， 招募现在活跃的P-TEFb到HIV LTR。迄今为止，只有富含达特烟碱的 已经解决了基序（ARM）肽-TAR RNA和乙酰氨基胍-TAR二元复合物。达特在 HARC中心旨在确定Tat-P-TEFb-TAR复合物的结构，以及 最小的Tat-CycT 1嵌合体与TAR和LC结合。这些结构将与那些达特- TAR复合物，以确定结合表面和结合构象的相似性和差异 为了更好地理解诱导契合在达特函数中的假定作用。

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.