Modeling and solution structure probing of the HIV-1 TAR stem-loop

Abstract

We present a model for the three-dimensional structure of the HIV TAR stem-loop, 1 based on a modeling algorithm 2 which makes use of the known X-ray coordinates of tRNAs to generate a model structure, which has then been tested experimentally in solution by enzymatic and chemical structure probing 3-5 of ribo-oligonucleotides encompassing the TAR sequence. The modeling suggested that the structure of TAR was similar to that of the anti-codon loop of tRNA Asp, having a loop of just three single-stranded residues with a mismatched adenine excluded from the helical stem on the 3' side of the loop. 6 The structural probing is consistent with such a structure for the loop, and reveals an unusual structure around the 5' undine-rich bulge, which is the binding target for the transactivator protein Tat. 7 These data may be useful in understanding the interaction of TAR with the Tat protein and may aid in the design of anti-AIDS drugs. The coordinates of the model are available on request.