The helix-to-sheet transition of an HIV-1 fusion peptide derivative changes the mechanical properties of lipid bilayer membranes.

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  • Author(s): Heller WT;Heller WT; Zolnierczuk PA; Zolnierczuk PA
  • Source:
    Biochimica et biophysica acta. Biomembranes [Biochim Biophys Acta Biomembr] 2019 Mar 01; Vol. 1861 (3), pp. 565-572. Date of Electronic Publication: 2018 Dec 12.
  • Publication Type:
    Journal Article; Research Support, U.S. Gov't, Non-P.H.S.
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Elsevier Country of Publication: Netherlands NLM ID: 101731713 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-2642 (Electronic) Linking ISSN: 00052736 NLM ISO Abbreviation: Biochim Biophys Acta Biomembr Subsets: MEDLINE
    • Publication Information:
      Original Publication: Amsterdam : Elsevier
    • Subject Terms:
      Biomechanical Phenomena/*physiology ; HIV Envelope Protein gp41/*chemistry ; Lipid Bilayers/*chemistry ; Membrane Fusion/*drug effects; Amino Acid Sequence ; Cell Membrane/drug effects ; Cell Membrane/physiology ; Circular Dichroism ; Dynamic Light Scattering ; HIV Envelope Protein gp41/pharmacology ; HIV-1/physiology ; Humans ; Lipid Bilayers/metabolism ; Magnetic Resonance Spectroscopy ; Membrane Fluidity/drug effects ; Membrane Fusion/genetics ; Models, Molecular ; Peptides/chemistry ; Peptides/pharmacology ; Protein Structure, Secondary/physiology ; Structure-Activity Relationship
    • Abstract:
      A short sequence on the gp41 envelope protein of HIV-1 is integral to infection by the virus. Without this sequence, termed the fusion peptide (FP), the virus is far less effective at fusing with the cellular membrane. One of the interesting features of the isolated FP is that it transitions between an α-helical conformation and a β-sheet conformation in lipid bilayer membranes as a function of lipid composition and concentration, and the transition correlates with fusion. To better understand how the conformations of the FP impact lipid bilayer membranes, a variant of the FP that does not strongly promote fusion, termed gp41rk, was studied. Circular dichroism spectroscopy, dynamic light scattering, small-angle neutron scattering (SANS) and neutron spin echo spectroscopy (NSE) were used to relate the conformation of gp41rk to the structure and mechanical properties of lipid bilayer membrane vesicles composed of a 7:3 molar ratio mixture of 1,2-dimyristoyl-sn-glycero-3-phosphocholine and 1,2-dimyristoyl-sn-glycero-3-phospho-(1'-rac-glycerol). At a peptide-to-lipid ratio (P/L) of 1/200, it adopts an α-helical conformation, while gp41rk is a β-sheet at a P/L of 1/50 in the unilamellar vesicles. SANS reveals that the lipid bilayer membrane becomes thicker when gp41rk adopts a β-sheet conformation, which indicates that the high-concentration state of the peptide increases the order of the lipid acyl chains. At the same time, NSE demonstrates that the bilayer becomes more rigid, demonstrating that the β-sheet conformation, which correlates with fusion for the native FP sequence, stiffens the bilayer. The results have implications for the function of the FP.
      (Copyright © 2018 Elsevier B.V. All rights reserved.)
    • Contributed Indexing:
      Keywords: Bilayer dynamics; HIV-1 fusion peptide; Membrane rigidity; Neutron spin echo spectroscopy
    • Accession Number:
      0 (HIV Envelope Protein gp41)
      0 (Lipid Bilayers)
      0 (Peptides)
    • Publication Date:
      Date Created: 20181215 Date Completed: 20191104 Latest Revision: 20191104
    • Publication Date:
      20240829
    • Accession Number:
      10.1016/j.bbamem.2018.12.004
    • Accession Number:
      30550881