Solid-state nuclear magnetic resonance evidence for an extended beta strand conformation of the membrane-bound HIV-1 fusion peptide

Solid-state nuclear magnetic resonance (NMR) spectroscopy was applied to th e membrane-bound form of a synthetic peptide representing the 23-residue N- terminal fusion peptide domain of the HIV-1 gp41 envelope glycoprotein, 1D solid-state NMR line width measurements of singly C-13 carbonyl labeled pep tides showed that a significant population of the membrane-bound peptide is well-structured in its N-terninal and central regions while the C-terminus has more disorder. There was some dependence of line width on lipid compos ition, with narrower line widths and hence greater structural order observe d for a lipid composition comparable to that found in the virus and its tar get T cells. In the more ordered N-terminal and central regions of the pept ide, the C-13 carbonyl chemical shifts are consistent with a nonhelical mem brane-bound conformation, Additional evidence for a beta strand membrane-bo und conformation was provided by analysis of 2D rotor-synchronized magic an gle spinning NMR spectra of doubly C-13 carbonyl labeled peptides, Lipid mi xing and aqueous contents leakage assays were applied to demonstrate the fu sogenicity of the peptide under conditions comparable to those used for the solid-state NMR sample preparation.