Instant Access to the Journals You Need

for just $40 per month.

Membrane-Perturbing Domains of HIV Type 1 Glycoprotein 41

Membrane-Perturbing Domains of HIV Type 1 Glycoprotein 41


Structural and functional studies were performed to assess the membrane actions of peptides based on HIV-1 glycoprotein 41,000 (gp41). Previous site-directed mutagenesis of gp41 has shown that amino acid changes in either the N-terminal fusion or N-leucine zipper region depressed viral infection and syncytium formation, while modifications in the C-leucine zipper domain both increased and decreased HIV fusion. Here, synthetic peptides were prepared corresponding to the N-terminal fusion region (FP-I; gp41 residues 519-541), the nearby N-leucine zipper domain (DP-107; gp41 residues 560-597), and the C-leucine zipper domain (DP-178; gp41 residues 645-680). With erythrocytes, FP-I or DP-107 induced dose-dependent hemolysis and promoted cell aggregation; FP-I was more hemolytic than DP-107, but each was equally effective in aggregating cells. DP-178 produced neither hemolysis nor aggregation, but blocked either FP-I- or DP-107-induced hemolysis and aggregation. Combined with previous nuclear magnetic resonance and Fourier transform infrared spectroscopic results, circular dichroism (CD) spectroscopy showed that the α-helicity for these peptides in solution decreased in the order: DP-107 >> DP-178 > FP-I. CD analysis also indicated binding of DP-178 to either DP-107 or FP-I. Consequently, DP-178 may inhibit the membrane actions mediated by either FP-I or DP-107 through direct peptide interactions in solution. These peptide results suggest that the corresponding N-terminal fusion and N-leucine zipper regions participate in HIV infection, by promoting membrane perturbations underlying the merging of the viral envelope with the cell surface. Further, the C-leucine zipper domain in "prefusion" HIV may inhibit these membrane activities by interacting with the N-terminal fusion and N-leucine zipper domains in unactivated gp41. Last, exogenous DP-178 may bind to the N-terminal and N-leucine zipper domains of gp41 that become exposed on HIV stimulation, thereby preventing the fusogenic actions of these gp41 regions leading to infection.
Loading next page...

You're reading a free preview. Sign up for Instant Access to thousands of journals for just $40/month.

By signing up, you agree to DeepDyve's Terms of Service and Privacy Policy.

What content is in DeepDyve?

  • Read and share from thousands of the leading scholarly journals from Springer, Elsevier, Nature, IEEE, Wiley-Blackwell and more.
  • All the latest content is available, no embargo periods.

Rent Scholarly Articles?

  • Read the full article in your browser.
  • Access all of your rentals from the cloud anywhere you have an internet connection.
  • Beautiful reading experience – Full charts and figures, just like the PDF.
  • Read as much as you'd like - whenever you'd like.

Happy Users

“In one word renting from DeepDyve is FANTASTIC!!! ... 99% of the time I only need access to an article for a month or so, so renting the articles is perfect for me.”

Adam S.

“Thanks for a great service! For an unaffiliated science blogger like myself this is like a dream come true.”

Seppo P.

“Hi guys, I cannot tell you how much I love this resource. Incredible. I really believe you've hit the nail on the head with this site in regards to solving the research-purchase issue.”

Daniel C.

“Let me seize this opportunity and congratulate you on the service you are rendering to the scientific community.”

Joao B.