Tat

Once the HIV genome is integrated into host DNA and ready for replication, the virus uses the regulatory protein Tat to enhance transcription from the viral promotor, by increasing processivity of RNA polymerase II (RNAP II) complexes. It does so by binding to an RNA site (TAR) on transcripts and recruiting other cellular proteins including the elongation factor P-TEFb, which is competed away from an alternate complex with HEXIM1-7SK snRNA.

The HARC Center Tat project, headed by Dr. Alan Frankel, extends and builds upon previous studies by Dr. Frankel and other HARC Center members on the Tat-TAR system, including extensive characterization of the involved proteins and structural efforts with outside collaborators that resulted in two atomic resolution structures of TAR RNA complexed with the arginine rich motif (ARM) of Tat or arginamide--the only structures of TAR binary complexes to date.

The Tat project relies upon the considerable resources within the center to express the necessary proteins and determine the structures of Tat with its nucleic acid and protein partners, using a variety of structural approaches. Ultimately, the goal is to understand the conformational changes that allow the various binding reactions, as well as the structural basis of transcriptional activation by Tat.