The amino-terminal peptide of HIV-1 glycoprotein 41 interacts with human erythrocyte membranes: peptide conformation, orientation and aggregation

• Published in: Biochimica et biophysica acta Vol. 1139; no. 4; p. 257
• Main Authors: Gordon, L M, Curtain, C C, Zhong, Y C, Kirkpatrick, A, Mobley, P W, Waring, A J
• Format: Journal Article
• Language: English
• Published: Netherlands 25-08-1992
• Subjects: Amino Acid Sequence; CD4-Positive T-Lymphocytes - cytology; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - metabolism; Circular Dichroism; Computer Simulation; Electron Spin Resonance Spectroscopy; Erythrocyte Membrane - metabolism; Fourier Analysis; Hemolysis; HIV Envelope Protein gp41 - chemistry; HIV Envelope Protein gp41 - metabolism; Humans; Melitten - pharmacology; Membrane Lipids - metabolism; Membrane Proteins - metabolism; Models, Chemical; Molecular Sequence Data; Peptide Fragments - chemistry; Peptide Fragments - metabolism; Protein Binding; Protein Conformation; Spectrophotometry, Infrared; Spin Labels
• ISSN: 0006-3002
• DOI: 10.1016/0925-4439(92)90099-9

Structural studies assessed interactions between the amino-terminal peptide (FP-I; 23 residues 519-541) of the glycoprotein 41,000 (gp41) of Human Immunodeficiency Virus Type-1 (HIV-1) and human erythrocyte membranes and simulated membrane environments. Peptide binding was examined at sub-hemolytic (approx. less than 5 microM) and hemolytic (greater than or equal to 5 microM) doses (Mobley et al. (1992) Biochem. Biophys. Acta 1139, 251-256), using circular dichroism (CD) and Fourier-transform infrared (FTIR) measurements with FP-I, and electron spin resonance (ESR) studies employing FP-I spin-labeled at either the amino-terminal alanine (FP-II; residue 519) or methionine (FP-III; position 537). In the sub-lytic regime, FP-I binds to both erythrocyte lipids and dispersions of SDS with high alpha-helicity. Further, ESR spectra of FP-II labeled erythrocyte ghosts indicated peptide binding to both lipid and protein. In ghost lipids, FP-II was monomeric and exhibited low polarity and rapid, anisotropic motion about its long molecular axis (i.e., alpha-helical axis), with restricted motion away from this axis. The spin-label at the amino-terminal residue (Ala-519) is insensitive to the aqueous broadening agent chromium oxalate and buried within the hydrophobic core of the membrane; the angle that the alpha-helix (residues 519-536) makes to the normal of the bilayer plane is either 0 degree or 40 degrees. Contrarily, ESR spectra of ghost lipids labeled with sub-lytic doses of FP-III indicated high mobility and polarity for the reporter group (Met-537) at the aqueous-membrane interface, as well as extreme sensitivity to chromium oxalate. At lytic FP-I doses, CD and FTIR showed both alpha-helix and beta-structure for peptide in ghost lipids or detergent, while ESR spectra of high-loaded FP-II in ghost membranes indicated peptide aggregates. Membrane aggregates of FP-I may be involved in hemolysis, and models are suggested for N-terminal gp41 peptide participation in HIV-induced fusion and cytolysis.