title: Membrane partitioning of the cleavage peptide in flock house virus.
abstract: Membrane translocation of the ssRNA genome of nodaviruses has been proposed to be mediated by direct lipid-protein interactions between a postassembly autocatalytic cleavage product from the capsomere and the target membrane. We have recently shown that the 21-residue Met-->Nle variant of the N-terminal helical domain (denoted gamma(1)) of the cleavage peptide in flock house nodavirus increases membrane permeability to hydrophilic solutes and can alter both membrane structure and function, suggesting the possibility of peptide-triggered disruption of the endosomal membrane as a prelude to viral uncoating in the host cytoplasm. Elucidation of partitioning energetics would allow an assessment of the likelihood of this mechanism. We report herein complete thermodynamic characterization of the partitioning of gamma(1) to phospholipids by lipid-peptide titrations following changes in ellipticity, fluorescence signature, or calorimetric response. These experiments revealed a partitioning energy comparable to natural membrane-active peptide toxins, suggesting that the proposed mechanism may be possible. Additionally, a novel switch in the balance of partitioning forces was found: when the lipid headgroup was changed from zwitterionic to negatively charged, membrane association of the peptide became completely entropy-driven.
authors.affiliation: Departments of Chemistry and Molecular Biology and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: D T
authors.initials: DT
authors.lastname: Bong
authors.forename: A
authors.initials: A
authors.lastname: Janshoff
authors.forename: C
authors.initials: C
authors.lastname: Steinem
authors.forename: M R
authors.initials: MR
authors.lastname: Ghadiri
mesh_terms: D000595:Amino Acid Sequence; D002151:Calorimetry; D002942:Circular Dichroism; D008081:Liposomes / Q000737:chemistry; D008563:Membrane Lipids / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D010743:Phospholipids / Q000737:chemistry; D017433:Protein Structure, Secondary; D012328:RNA Viruses / Q000737:chemistry*; D013050:Spectrometry, Fluorescence; D013816:Thermodynamics; D014764:Viral Proteins / Q000737:chemistry*
chemical_list: D008081:Liposomes; D008563:Membrane Lipids; D010455:Peptides; D010743:Phospholipids; D014764:Viral Proteins