IDENTIFICATION OF A MEMBRANE-BINDING DOMAIN WITHIN THE AMINO-TERMINALREGION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 GAG PROTEIN WHICH INTERACTS WITH ACIDIC PHOSPHOLIPIDS

Retroviral Gag proteins are targeted to the plasma membrane, where the y play the central role in virion formation. Several studies have sugg ested that the membrane-binding signal is contained within the amino-t erminal matrix sequence; however, the precise location has never been determined for the Gag protein of any retrovirus. In this report, we s how that the first 31 residues of human immunodeficiency virus type 1 Gag protein can function independently as a membrane-targeting domain when fused to heterologous proteins. A bipartite membrane-targeting mo tif was identified, consisting of the myristylated N-terminal 14 amino acids and a highly basic region that binds acidic phospholipids. Repl acement of the N-terminal membrane-targeting domain of pp60(v-src) wit h that of human immunodeficiency virus type 1 Gag elicits efficient me mbrane binding and a transforming phenotype. Removal of myristate or t he basic region results in decreased membrane binding of Gag-Src chime ras in vitro and impaired virion formation by Pr55(gag) in vivo. We pr opose that the N-terminal Gag sequence functions as a targeting signal to direct interaction with acidic phospholipids on the cytoplasmic le aflet of the plasma membrane.