NMR STRUCTURE OF A BIOLOGICALLY-ACTIVE PEPTIDE-CONTAINING THE RNA-BINDING DOMAIN OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 TAT

The Tat protein of human immunodeficiency virus type 1 enhances transc ription by binding to a specific RNA element on nascent viral transcri pts. Binding is mediated by a 10-amino acid basic domain that is rich in arginines and lysines. Here we report the three-dimensional peptide backbone structure of a biologically active 25-mer peptide that conta ins the human immunodeficiency virus type 1 Tat basic domain linked to the core regulatory domain of another lentiviral Tat-i.e., that from equine infectious anemia virus. Circular dichroism and two-dimensional proton NMR studies of this hybrid peptide indicate that the Tat basic domain forms a stable alpha-helix, whereas the adjacent regulatory se quence is mostly in extended form. These findings suggest that the ten dency to form stable alpha-helices may be a common property of arginin e- and lysine-rich RNA-binding domains.