Conformational transitions of membrane-bound HIV-1 fusion peptide.
The human immunodeficiency virus type-1 (HIV-1) fusion peptide (FP) functions as a non-constitutive membrane anchor that translocates into membranes during envelope glycoprotein-induced fusion. Here, by means of infrared spectroscopy (IR) and of various bilayer-perturbation assays, we describe the peptide conformations that are accessible to its membrane-bound state and the transitions occurring between them. The peptide underwent a conformational transition from a predominantly alpha-helical structure to extended beta-type strands by increasing peptide concentration in 1-palmitoyl-2-oleoylphosphatidylglycerol (POPG) vesicles. A comparable transition was observed at a fixed 1:100 peptide-to-lipid ratio when calcium was added to vesicles containing prebound alpha-helical peptide. Cation binding induced an increase in the amount of H-bonded carbonyls within the interfacial region of POPG. Calcium-promoted alpha-->beta conversion in membranes correlated with the closure of preformed lytic pores and took place in dispersed (nonaggregated) vesicles doped with poly(ethylene glycol)-lipid conjugates, showing that the conformational transition was independent of vesicle aggregation. We conclude that the target membrane conditions modulate the eventual structure adopted by the HIV-1 FP. Conformational polymorphism of the inserted peptide may contribute to the flexibility of the fusogenic complex during the fusion reaction cycle, and/or may be related to target membrane perturbation at the fusion locus.
Sáez-Cirión
Asier
A
Unidad de Biofísica (CSIC-UPV/EHU) and Departamento de Bioquímica, Universidad del País Vasco, Aptdo. 644, 48080 Bilbao, Spain.
Nieva
José L
JL
D000595:Amino Acid Sequence; D002118:Calcium / Q000494:pharmacology; D015700:HIV Envelope Protein gp41 / Q000737:chemistry / Q000235:genetics; D015497:HIV-1 / Q000737:chemistry* / Q000235:genetics; D006860:Hydrogen Bonding; D066298:In Vitro Techniques; D008081:Liposomes; D008561:Membrane Fusion; D008969:Molecular Sequence Data; D010715:Phosphatidylglycerols; D011487:Protein Conformation / Q000187:drug effects; D017433:Protein Structure, Secondary; D017550:Spectroscopy, Fourier Transform Infrared; D014760:Viral Fusion Proteins / Q000737:chemistry* / Q000235:genetics
D015700:HIV Envelope Protein gp41; D008081:Liposomes; D010715:Phosphatidylglycerols; D014760:Viral Fusion Proteins; C060037:1-palmitoyl-2-oleoylglycero-3-phosphoglycerol; D002118:Calcium