Identification of membrane-active regions of the HIV-1 envelope glycoprotein gp41 using a 15-mer gp41-peptide scan

• Published in: Biochimica et biophysica acta Vol. 1661; no. 1; pp. 97 - 105
• Main Authors: Moreno, Miguel R., Pascual, Roberto, Villalaín, José
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 10.02.2004
• Subjects: Animals; Binding Sites - genetics; Drug Design; gp41; HIV Envelope Protein gp41 - chemistry; HIV Envelope Protein gp41 - genetics; HIV Envelope Protein gp41 - metabolism; HIV Fusion Inhibitors; HIV-1; Liposomes - chemistry; Membrane fusion; Membrane Fusion - drug effects; Membranes - chemistry; Membranes - drug effects; Membranes - metabolism; Models, Molecular; Peptide Library; Peptides - genetics; Peptides - pharmacology; Phosphatidylserines; Protein Structure, Tertiary; Sphingomyelins; Virus-cell entry; HIV-1; Membrane fusion; Chol; CF; PS; gp; PSM; CHR; LUV; Virus-cell entry; PA; PC; PE; gp41; POPC; NHR; PI; Tm; SM
• ISSN: 0005-2736; 0006-3002; 1879-2642
• DOI: 10.1016/j.bbamem.2003.12.003

The identification of membrane-active regions of the ectodomain of the HIV-1 envelope glycoprotein gp41 has been made by determining the effect on membrane integrity of a 15-mer gp41-derived peptide library. By monitoring the effect of this peptide library on membrane leakage, we have identified three regions on the gp41 ectodomain with membrane-interacting capabilities: Region 1, which would roughly correspond to the polar sequence which follows the fusion domain and extends to the N-terminal heptad repeat region; Region 2, which would correspond to the immunodominant loop; and Region 3, which would correspond to the pre-transmembrane region of gp41. The identification of these three regions supports their direct role in membrane fusion as well as facilitating the future development of HIV-1 entry inhibitors.