人免疫缺陷病毒（HIV）的Tat蛋白很多年来一直是结构研究的一个目标，人们期望由此找到可能的治疗干预方法。Tat在感染初期具有活性，“劫持”宿主的正转录伸长因子P-TEFb。后者对于一个宿主蛋白来说是不寻常的，因此也是一个潜在的药物作用目标。

　　Tahirov等人报告了HIV Tat在与P-TEFb所形成的复合物中的第一个晶体结构。这一2.1-A分辨率的晶体结构显示，尽管Tat 和 P-TEFb之间的互动界面很大，但Tat的结合会改变P-TEFb的结构。这一发现为开发只阻断被病毒所利用的那种P-TEFb形式的抑制剂指出了可能的机会。

 

生物谷推荐原文出处：

Nature  doi:10.1038/nature09131

Crystal structure of HIV-1 Tat complexed with human P-TEFb
Tahir H. Tahirov1, Nigar D. Babayeva1, Katayoun Varzavand2, Jeffrey J. Cooper2, Stanley C. Sedore2 & David H. Price2

1 Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska 68198-7696, USA
2 Biochemistry Department, University of Iowa, Iowa City, Iowa 52242, USA

Regulation of the expression of the human immunodeficiency virus (HIV) genome is accomplished in large part by controlling transcription elongation. The viral protein Tat hijacks the host cell’s RNA polymerase II elongation control machinery through interaction with the positive transcription elongation factor, P-TEFb, and directs the factor to promote productive elongation of HIV mRNA. Here we describe the crystal structure of the Tat·P-TEFb complex containing HIV-1 Tat, human Cdk9 (also known as CDK9), and human cyclin T1 (also known as CCNT1). Tat adopts a structure complementary to the surface of P-TEFb and makes extensive contacts, mainly with the cyclin T1 subunit of P-TEFb, but also with the T-loop of the Cdk9 subunit. The structure provides a plausible explanation for the tolerance of Tat to sequence variations at certain sites. Importantly, Tat induces significant conformational changes in P-TEFb. This finding lays a foundation for the design of compounds that would specifically inhibit the Tat·P-TEFb complex and block HIV replication.