title: Role of sequence and structure of the Hendra fusion protein fusion peptide in membrane fusion.
abstract: Viral fusion proteins are intriguing molecular machines that undergo drastic conformational changes to facilitate virus-cell membrane fusion. During fusion a hydrophobic region of the protein, termed the fusion peptide (FP), is inserted into the target host cell membrane, with subsequent conformational changes culminating in membrane merger. Class I fusion proteins contain FPs between 20 and 30 amino acids in length that are highly conserved within viral families but not between. To examine the sequence dependence of the Hendra virus (HeV) fusion (F) protein FP, the first eight amino acids were mutated first as double, then single, alanine mutants. Mutation of highly conserved glycine residues resulted in inefficient F protein expression and processing, whereas substitution of valine residues resulted in hypofusogenic F proteins despite wild-type surface expression levels. Synthetic peptides corresponding to a portion of the HeV F FP were shown to adopt an α-helical secondary structure in dodecylphosphocholine micelles and small unilamellar vesicles using circular dichroism spectroscopy. Interestingly, peptides containing point mutations that promote lower levels of cell-cell fusion within the context of the whole F protein were less α-helical and induced less membrane disorder in model membranes. These data represent the first extensive structure-function relationship of any paramyxovirus FP and demonstrate that the HeV F FP and potentially other paramyxovirus FPs likely require an α-helical structure for efficient membrane disordering and fusion.
authors: Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY 40536, USA.
authors: Everett Clinton
authors: EC
authors: Smith
authors: Sonia M
authors: SM
authors: Gregory
authors: Lukas K
authors: LK
authors: Tamm
authors: Trevor P
authors: TP
authors: Creamer
authors: Rebecca Ellis
authors: RE
authors: Dutch
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D002522:Chlorocebus aethiops; D002942:Circular Dichroism; D008561:Membrane Fusion; D020125:Mutation, Missense; D010252:Paramyxoviridae / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017433:Protein Structure, Secondary; D013329:Structure-Activity Relationship; D014709:Vero Cells; D014760:Viral Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D014760:Viral Fusion Proteins