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M9490429.TXT
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1994-09-19
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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).