A 1.3-ANGSTROM RESOLUTION CRYSTAL-STRUCTURE OF THE HIV-1 TRANSACTIVATION RESPONSE REGION RNA STEM REVEALS A METAL ION-DEPENDENT BULGE CONFORMATION

The crystal structure of an HIV-1 transactivation response region (TAR ) RNA fragment containing the binding site for the trans-activation pr otein Tat has been determined to 1.3-Angstrom resolution. In this crys tal structure, the characteristic UCU bulge of TAR adopts a conformati on that is stabilized by three divalent calcium ions and differs from those determined previously by solution NMR. One metal ion, crucial to the loop conformation, binds directly to three phosphates in the loop region. The structure emphasizes the influence of metal ion binding o n RNA structure and, given the abundance of divalent metal ion in the cell, raises the question of whether metal ions play a role in the con formation of TAR RNA and the interaction of TAR with Tat and cyclin T in vivo.