Identification of a calmodulin-binding and inhibitory peptide domain in the HIV-1 transmembrane glycoprotein

M. A. Miller, T. A. Mietzner, M. W. Cloyd, W. G. Robey, R. C. Montelaro

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1057-1066
Number of pages10
JournalAIDS Research and Human Retroviruses
Volume9
Issue number11
StatePublished - 1993

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Calmodulin
HIV-1
Glycoproteins
Proteins
Peptides
Protein Domains
Phosphoric Diester Hydrolases
Signal Transduction
Phospholipids
Cell Culture Techniques
Cell Membrane
HIV
Calcium
Amino Acids
Membranes

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Miller, M. A., Mietzner, T. A., Cloyd, M. W., Robey, W. G., & Montelaro, R. C. (1993). Identification of a calmodulin-binding and inhibitory peptide domain in the HIV-1 transmembrane glycoprotein. AIDS Research and Human Retroviruses, 9(11), 1057-1066.

Identification of a calmodulin-binding and inhibitory peptide domain in the HIV-1 transmembrane glycoprotein. / Miller, M. A.; Mietzner, T. A.; Cloyd, M. W.; Robey, W. G.; Montelaro, R. C.

In: AIDS Research and Human Retroviruses, Vol. 9, No. 11, 1993, p. 1057-1066.

Research output: Contribution to journalArticle

Miller, MA, Mietzner, TA, Cloyd, MW, Robey, WG & Montelaro, RC 1993, 'Identification of a calmodulin-binding and inhibitory peptide domain in the HIV-1 transmembrane glycoprotein', AIDS Research and Human Retroviruses, vol. 9, no. 11, pp. 1057-1066.
Miller, M. A. ; Mietzner, T. A. ; Cloyd, M. W. ; Robey, W. G. ; Montelaro, R. C. / Identification of a calmodulin-binding and inhibitory peptide domain in the HIV-1 transmembrane glycoprotein. In: AIDS Research and Human Retroviruses. 1993 ; Vol. 9, No. 11. pp. 1057-1066.
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