title: Membrane curvature and surface area per lipid affect the conformation and oligomeric state of HIV-1 fusion peptide: a combined FTIR and MD simulation study.
abstract: Fourier-transformed infrared spectroscopy (FTIR) and molecular dynamics (MD) simulation results are presented to support our hypothesis that the conformation and the oligomeric state of the HIV-1 gp41 fusion domain or fusion peptide (gp41-FP) are determined by the membrane surface area per lipid (APL), which is affected by the membrane curvature. FTIR of the gp41-FP in the Aerosol-OT (AOT) reversed micellar system showed that as APL decreases from approximately 50 to 35 A2 by varying the AOT/water ratio, the FP changes from the monomeric alpha-helical to the oligomeric beta-sheet structure. MD simulations in POPE lipid bilayer systems showed that as the APL decreases by applying a negative surface tension, helical monomers start to unfold into turn-like structures. Furthermore, an increase in the applied lateral pressure during nonequilibrium MD simulations favored the formation of beta-sheet structure. These results provide better insight into the relationship between the structures of the gp41-FP and the membrane, which is essential in understanding the membrane fusion process. The implication of the results of this work on what is the fusogenic structure of the HIV-1 FP is discussed.
authors.affiliation: Department of Physics and Astronomy, University of Missouri-Columbia, Columbia, MO 65211, USA.
authors.forename: Bogdan
authors.initials: B
authors.lastname: Barz
authors.forename: Tuck C
authors.initials: TC
authors.lastname: Wong
authors.forename: Ioan
authors.initials: I
authors.lastname: Kosztin
mesh_terms: D003198:Computer Simulation; D015700:HIV Envelope Protein gp41 / Q000737:chemistry*; D006860:Hydrogen Bonding; D008051:Lipid Bilayers / Q000737:chemistry*; D008055:Lipids / Q000737:chemistry*; D008958:Models, Molecular; D010455:Peptides; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017550:Spectroscopy, Fourier Transform Infrared; D013997:Time Factors
chemical_list: D015700:HIV Envelope Protein gp41; D008051:Lipid Bilayers; D008055:Lipids; D010455:Peptides