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A tyrosine-sulfated CCR5-mimetic peptide promotes conformational transitions in the HIV-1 envelope glycoprotein

Academic Article
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Overview

authors

  • Kwong, J. A.
  • Dorfman, T.
  • Quinlan, B. D.
  • Chiang, J. J.
  • Ahmed, A. A.
  • Choe, Hyeryun
  • Farzan, Michael

publication date

  • August 2011

journal

  • Journal of Virology  Journal

abstract

  • The HIV-1 envelope glycoprotein is a trimeric complex of heterodimers composed of a surface glycoprotein, gp120, and a transmembrane component, gp41. The association of this complex with CD4 stabilizes the coreceptor-binding site of gp120 and promotes the exposure of the gp41 helical region 1 (HR1). Here, we show that a 15-amino-acid peptide mimetic of the HIV-1 coreceptor CCR5 fused to a dimeric antibody Fc domain (CCR5mim-Ig) bound two gp120 molecules per envelope glycoprotein complex and by itself promoted HR1 exposure. CCR5mim-Ig also stabilized the association of a CD4-mimetic peptide with the envelope glycoprotein. A fusion of the CD4- and CCR5-mimetic peptides, DM1, bound gp120 and neutralized R5, R5X4, and X4 HIV-1 isolates comparably to CD4, and they did so markedly more efficiently than either peptide alone. Our data indicate that the potency of DM1-Ig derives from its avidity for the HIV-1 envelope glycoprotein trimer and from the bidirectional induction of its receptor-mimetic components. DM1 has significant advantages over other inhibitors that target both coreceptor and CD4-binding sites, and it may serve as a lead for a new class of HIV-1 inhibitor peptides.

subject areas

  • Cell Line
  • Flow Cytometry
  • HIV Envelope Protein gp120
  • HIV Envelope Protein gp41
  • HIV-1
  • Humans
  • Models, Molecular
  • Molecular Mimicry
  • Protein Conformation
  • Receptors, CCR5
  • Sulfates
  • Tyrosine
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Identity

PubMed Central ID

  • PMC3147930

International Standard Serial Number (ISSN)

  • 0022-538X

Digital Object Identifier (DOI)

  • 10.1128/jvi.00630-11

PubMed ID

  • 21613393
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Additional Document Info

start page

  • 7563

end page

  • 7571

volume

  • 85

issue

  • 15

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