Document 0348
 DOCN  M9440348
 TI    Identification of a calmodulin-binding and inhibitory peptide domain in
       the HIV-1 transmembrane glycoprotein.
 DT    9404
 AU    Miller MA; Mietzner TA; Cloyd MW; Robey WG; Montelaro RC; Department of
       Molecular Genetics and Biochemistry, University of; Pittsburgh School of
       Medicine, Pennsylvania 15261.
 SO    AIDS Res Hum Retroviruses. 1993 Nov;9(11):1057-66. Unique Identifier :
       AIDSLINE MED/94145739
 AB    A number of studies suggest a critical role of the HIV-1 envelope
       glycoprotein in cytopathogenesis, but the detailed mechanisms of cell
       injury remain to be defined. HIV-1 envelope proteins associate with the
       host cell membrane, and studies have demonstrated that HIV perturbs
       membrane structure and function. We describe here a structurally
       conserved region of the HIV-1 transmembrane protein (TM) that displays
       functional properties of target regions of proteins that interact
       directly with calcium-saturated calmodulin as part of cellular response
       cascades. The synthetic peptide homolog encompassing the carboxyl
       terminus (amino acid residues 828-855) of HIV-1 TM protein (LLP-1) is
       shown in standard in vitro assays to bind efficiently to purified
       calmodulin (CaM) and to inhibit in vitro CaM-mediated stimulation of
       phosphodiesterase activity. This suggests that this peptide homolog
       binds to CaM at affinities similar to those reported for a reference
       CaM-binding peptide. In addition, the CaM-dependent process of
       phospholipid synthesis can be inhibited in cell cultures by exogenous
       addition of the LLP-1. Finally, we have shown that the full-length TM
       protein binds CaM, whereas a truncated TM protein lacking the LLP-1
       segment does not bind CaM. These results suggest a novel mechanism of
       viral cytopathogenesis mediated by the interaction of HIV-1 TM protein
       with cellular CaM, that could lead to an uncoupling of critical cellular
       signal transduction pathways.
 DE    Amino Acid Sequence  Binding Sites/GENETICS  Calmodulin/*METABOLISM
       Cell Line  Cytopathogenic Effect, Viral/GENETICS/PHYSIOLOGY  Gene
       Products, env/GENETICS/*METABOLISM  Human
       HIV-1/GENETICS/*METABOLISM/PATHOGENICITY  Molecular Sequence Data
       Peptide Fragments/CHEMICAL SYNTHESIS/GENETICS/METABOLISM
       Phospholipids/BIOSYNTHESIS  Phosphoric Diester Hydrolases/METABOLISM
       Signal Transduction/GENETICS/PHYSIOLOGY  Support, Non-U.S. Gov't
       Support, U.S. Gov't, P.H.S.  JOURNAL ARTICLE

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