Participation of Two Fusion Peptides in Measles Virus-Induced Membrane Fusion:  Emerging Similarity with Other Paramyxoviruses

Abstract

Paramyxoviruses penetrate into their host cells by fusing their membranes with the plasma membrane. The hydrophobic N terminus of their F1 protein, termed the 'fusion peptide', is thought to be responsible for this process. Recently, an additional internal fusion peptide, homologous in sequence to the N-terminal fusion peptide of HIV-1, was identified in the Sendai virus F1 protein. Here, we investigated whether the presence of an additional internal fusion peptide is a general feature of paramyxoviridae. To this end, we synthesized and structurally and functionally characterized three peptides: (i) MV-197, which corresponds to an internal segment of the F1 protein of the measles virus (amino acids 197-225), homologous in location but not in sequence to the internal fusion peptide of the Sendai virus, (ii) Mu-MV-197, a randomized version of MV-197, and (iii) the 33 amino acid N-terminal fusion peptide of the measles virus. Remarkably, only MV-197 was highly fusogenic toward large unilamellar vesicles composed of either zwitterionic (phosphatidylcholine or phosphatidylcholine/sphingomyelin/cholesterol, a composition similar to that of human cell membranes) or negatively charged phospholipids. Binding experiments, circular dichroism spectroscopy in phospholipid membranes, and homo energy-transfer studies with fluorescently labeled peptides revealed that MV-197 adopts a predominant alpha-helical structure and shares properties similar to those reported for known fusion peptides. These results suggest that the presence of two fusion peptides in the F1 protein is a general feature of paramyxoviruses.

How Structure Correlates to Function for Membrane Associated HIV-1 gp41 Constructs Corresponding to the N-terminal Half of the Ectodomain

“…It should be noted that a target membrane composition similar to that used here gave parallel results in comparison to PC LUV for the measles virus internal FP. 49 Together, these results support the idea that PC closely models the outer target membrane due likely to its zwitterionic character and the fact that it shares a head group with sphingomyelin, both of which comprise a significant majority of total outer leaflet phospholipids in the target membrane (reviewed in Refs. 47,48).…”

Enhanced Delivery of Exogenous Peptides into the Class I Antigen Processing and Presentation Pathway

“…This segment is part of a 36-amino-acid hairpin-like structure, consisting of two helical regions interrupted by a flexible loop region that contains two glutamate residues (4, 9). The Pol segment used in the present study contains the two glutamates and the flexible region composed of hydrophobic and nonpolar amino acids and shows a degree of similarity with fusion peptides from viral glycoproteins (29). Therefore, one explanation for the improved delivery of the SIINFEKL epitope by peptides containing the Pol loop segment may be that this segment has an intrinsic propensity to penetrate lipid bilayers.…”

Toward Preserving the Structure of the Antigenic Peptide p17-1 from the HIV-1 p17 Protein in Nanostructured Films

“…[8][9][10][11][12][13][14][15] Antigenic peptides are a sequence of amino acids (epitopes) of an antigen which are able to recognize specific antibodies. 16 These peptides can be determined by mapping epitopes 17 and be prepared with high purity via chemical synthesis.…”