3-DIMENSIONAL STRUCTURE AND ANTIGENICITY OF TRANSMEMBRANE-PROTEIN PEPTIDES OF THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 - EFFECTS OF A NEUTRALIZATION-ESCAPE SUBSTITUTION

A point mutation (Ala-589 to Thr) in the transmembrane protein of the human immunodeficiency virus type 1 (HIV-1) has been shown to decrease the sensitivity of the virus to the neutralizing effect of human HIV- 1 specific antibodies [(1990) J. Virol. 64, 3240-3248]. Here 17-residu e peptides with the parental and mutant sequences were compared: the p arental peptide bound antibodies of sera from HIV-1 infected persons m ore frequently and with higher affinity than the mutant peptide. Howev er, according to circular dichroism (CD), NMR spectroscopy and molecul ar modelling the peptides have indistinguishable backbone conformation s under a variety of experimental conditions. These techniques showed for both peptides that no ordered helix was present in water solution. However, for both peptides in alcohol-water solutions approximately 6 0% alpha-helix could be induced. The three-dimensional structures of t hese peptides provide a basis for understanding how this mutation in t he transmembrane protein may affect the interaction with both the oute r envelope glycoprotein and with antibodies.