CRYSTALLIZATION STUDIES OF THE HUMAN-IMMUNODEFICIENCY-VIRUS (HIV-1) TAT PROTEIN AND ITS TRANSACTIVATION RESPONSE ELEMENT (TAR) RNA

Small single crystals are reported of a complex between a small peptid e fragment of the HIV-1 Tat protein and a fragment of the RNA to which it binds. Tat is responsible for enhancing the level of expression of the human immunodeficiency virus type 1 (HIV-1) and is a logical targ et for AIDS therapy. Tat may function to increase the level of transcr iption initiation or to prevent premature termination of transcripts. In vitro, Tat binds through its basic domain (two Lys and six Arg in n ine residues) to a three-nucleotide bulge of a stem-loop RNA structure called TAR. Complex formation between Tat and TAR is necessary for Ta t activity. Peptides which contain the basic region of Tat also bind t o TAR RNA. We have carried out crystallization experiments on a 27-nuc leotide fragment of TAR RNA and on complexes between two Tat peptides and TAR.