Document 0429
 DOCN  M9490429
 TI    Myristoylation-dependent binding of HIV-1 Nef to CD4.
 DT    9411
 AU    Harris MP; Neil JC; Department of Veterinary Pathology, University of
       Glasgow,; Scotland, U.K.
 SO    J Mol Biol. 1994 Aug 12;241(2):136-42. Unique Identifier : AIDSLINE
       MED/94334972
 AB    The nef gene is conserved throughout the primate lentivirus family.
       Although dispensable in vitro, an important role for nef in vivo is
       suggested by the failure of SIV nef mutants to establish persistent
       viraemia. Although the biochemical function of the Nef protein remains
       equivocal, a consistent theme has emerged with the reproducible
       observation that Nef expression results in the down-modulation of the
       cell surface marker CD4. Down-modulation requires amino acid sequences
       within the cytoplasmic domain of CD4 but occurs by a mechanism distinct
       from the normal serine phosphorylation-dependent pathway. As CD4 is a
       transmembrane glycoprotein and Nef a myristoylated protein targeted to
       the cytoplasmic face of the plasma membrane we considered that a direct
       interaction between Nef and CD4 might play a role in down-modulation.
       Here we demonstrate that a baculovirus-expressed Nef-GST fusion protein
       interacts specifically with CD4. This interaction requires co-expression
       in the same cell and is dependent on Nef myristoylation. The site of Nef
       interaction maps to the cytoplasmic domain of CD4, as a deletion mutant
       lacking this domain fails to interact with Nef. This observation sheds
       new light on the biochemical function of Nef and offers new
       opportunities for the future development of HIV chemotherapy.
 DE    Animal  Antigens, CD4/GENETICS/*METABOLISM  Base Sequence  Binding Sites
       Cell Line  Down-Regulation (Physiology)  Flow Cytometry  Gene Products,
       nef/*METABOLISM  Genes, nef  Human  *HIV-1  Immunoblotting  Mice
       Molecular Sequence Data  Myristates/METABOLISM  Recombinant Fusion
       Proteins/METABOLISM  Support, Non-U.S. Gov't  SIV/GENETICS/METABOLISM
       JOURNAL ARTICLE

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