The amino-terminal fusion domain peptide of human immunodeficiency virus type 1 gp41 inserts into the sodium dodecyl sulfate micelle primarily as a helix with a conserved glycine at the micelle-water interface.
A peptide based on the N-terminal fusion domain of gp41 of human immunodeficiency virus type 1 (HIV-1) and its tryptophan analog were synthesized to examine the secondary structure in the micellar environment. Nuclear magnetic resonance (NMR), circular dichroism and electron paramagnetic resonance experiments indicated that the gp41 fusion peptide inserted into the micelle primarily as a helix (59%), with substantial beta-structure (26.7%). Deep penetration of the peptide into the apolar hydrocarbon core was supported by the results of fluorescence experiments in which the tryptophan analog exhibited a blue shift of about 30 nm in the presence of a sodium dodecyl sulfate micelle, in 1,2-dimyristoyl-rac-glycero-3-phosphocholine, and in 1,2-dipalmitoyl-sn-glycero-3-phospho-L-serine vesicular solutions. The results of spin label-attenuated 1H resonance experiments show that the region C-terminal to G16, which contains a turn structure, exhibited substantial interaction with the micelle, suggesting that it lies on the surface of micelle. Molecular simulation based on data from NMR experiments revealed a flexible hinge at residues 15 and 16 (alanine and glycine, respectively) from the N terminus of the peptide located at the micelle-solution interface. The highly conserved A15-G16 dipeptide may play a role in the function of fusion domain of HIV-1 envelope glycoprotein.
Chang
D K
DK
Institute of Chemistry, Academia Sinica, Taipei, Taiwan, Republic of China. dkc@chem.sinica.edu.tw
Cheng
S F
SF
Chien
W J
WJ
D000595:Amino Acid Sequence; D001665:Binding Sites; D002942:Circular Dichroism; D017124:Conserved Sequence; D004578:Electron Spin Resonance Spectroscopy; D005453:Fluorescence; D005998:Glycine / Q000737:chemistry*; D015700:HIV Envelope Protein gp41 / Q000737:chemistry*; D015497:HIV-1 / Q000737:chemistry*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D010743:Phospholipids; D017433:Protein Structure, Secondary; D011522:Protons; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry; D012996:Solutions; D013113:Spin Labels; D014867:Water
D015700:HIV Envelope Protein gp41; D008823:Micelles; D010455:Peptides; D010743:Phospholipids; D011522:Protons; D012996:Solutions; D013113:Spin Labels; D014867:Water; D012967:Sodium Dodecyl Sulfate; D005998:Glycine