Experiments have been done on the structure of a number of proteins involved in HIV transcription, encapsidation and budding. The high resolution three-dimensional structure of a synthetic 57-residue peptide comprising the double zinc finger of the human enhancer binding protein, MBP- 1, has been determined by NMR. Each finger comprises an irregular anti-parallel beta-sheet and an alpha-helix, with the zinc tetrahedrally coordinated to two cysteines and two histidines. Comparison of the structure of MBP- 1 with the x-ray structure of the Zif-268 triple finger complexed with DNA indicates that the relative orientations of the individual zinc fingers are distinct. Peptides of 39 and 55 residues containing the two zinc binding domains of the p7 nucleocapsid protein have been characterized by physicochemical and nucleic acid binding analyses. Fluorescence and circular dichroism studies demonstrated that the unstructured apo-peptides assume an ordered conformation in the presence of zinc. Computational analysis of a region near the 5' end of the HIV- 1 genome revealed a pair of stem-loops separated by 9 and 13 bases. This structure is the binding site of the p7 nucleocapsid protein. Recently, separate studies indicated strong cellular immunity against HIV- 1. Cytotoxic T-cells that recognize peptide fragments bound to major histocompatibility complex (MHC) Class I molecules have been identified. The sequence analysis of these peptides should permit the identification of viral epitopes capable of eliciting cellular cytotoxic responses and prove valuable in the development of a vaccine.
