Computer analysis of human immunodeficiency virus-1 envelope glycoprotein: Functional topogenic domains as signals for transfer and cleavage

Abstract

Analysis of human immunodeficiency virus-1 (HIV-1) gp160 amino acid sequences by computer programs that provide information on the possible conformation, hydrophilicity, and surface probability was used to identify possible functional domains. Amino acid domains that serve as signals for transfer of the polypeptide chain through the cell membrane were identified. Stop-transfer amino acid domains present in gp160 made possible the identification of the membrane anchorage hydrophobic amino acid sequence. The characterization of amino acid domains that serve as signals for proteolytic cleavage suggest that gp41 might be cleaved in a number of positions in the polypeptide chain, releasing parts of the carboxy-terminus amino acid sequence from that part of gp41 anchored in the cell membrane. The computer analysis deals with the mode of insertion of gp160 into the cell membrane by the cellular signal recognition protein system and subsequent processing of the gp160 to gp120 and gp41 (and subpeptides). The model for the positioning of these peptides is used to predict the organization of the processed envelope proteins in the viral envelope. The possible function of domains in gp120 and gp41 during the interaction with host cells during virus infection is discussed.