Document 0104
 DOCN  M9460104
 TI    Identification of a membrane-binding domain within the amino-terminal
       region of human immunodeficiency virus type 1 Gag protein which
       interacts with acidic phospholipids.
 DT    9404
 AU    Zhou W; Parent LJ; Wills JW; Resh MD; Cell Biology and Genetics Program,
       Memorial Sloan-Kettering; Cancer Center, New York, New York 10021.
 SO    J Virol. 1994 Apr;68(4):2556-69. Unique Identifier : AIDSLINE
       MED/94187097
 AB    Retroviral Gag proteins are targeted to the plasma membrane, where they
       play the central role in virion formation. Several studies have
       suggested that the membrane-binding signal is contained within the
       amino-terminal matrix sequence; however, the precise location has never
       been determined for the Gag protein of any retrovirus. In this report,
       we show 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
       motif was identified, consisting of the myristylated N-terminal 14 amino
       acids and a highly basic region that binds acidic phospholipids.
       Replacement of the N-terminal membrane-targeting domain of pp60v-src
       with that of human immunodeficiency virus type 1 Gag elicits efficient
       membrane binding and a transforming phenotype. Removal of myristate or
       the basic region results in decreased membrane binding of Gag-Src
       chimeras in vitro and impaired virion formation by Pr55gag in vivo. We
       propose that the N-terminal Gag sequence functions as a targeting signal
       to direct interaction with acidic phospholipids on the cytoplasmic
       leaflet of the plasma membrane.
 DE    Acids/METABOLISM  Amino Acid Sequence  Base Sequence  Biological
       Transport  Cell Compartmentation  Cell Membrane/METABOLISM  Cell
       Transformation, Neoplastic  Chimeric Proteins/METABOLISM  Comparative
       Study  Gene Products, gag/GENETICS/*METABOLISM  Human  HIV-1/*GROWTH &
       DEVELOPMENT  Molecular Sequence Data  Myristic Acids/METABOLISM
       Oncogene Protein pp60(v-src)/GENETICS/METABOLISM
       Phospholipids/*METABOLISM  Protein Binding  Protein
       Precursors/GENETICS/METABOLISM  Protein Processing, Post-Translational
       Structure-Activity Relationship  Support, Non-U.S. Gov't  Support, U.S.
       Gov't, P.H.S.  Tetrahydrofolate Dehydrogenase/GENETICS/METABOLISM
       JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).