Identification of the HIV-1 gp41 core-binding motif--HXXNPF.
The HIV-1 gp41 core, a six-helix bundle formed between the N- and C-terminal heptad repeats, plays a critical role in fusion between the viral and target cell membranes. Using N36(L8)C34 as a model of the gp41 core to screen phage display peptide libraries, we identified a common motif, HXXNPF (X is any of the 20 natural amino acid residues). A selected positive phage clone L7.8 specifically bound to N36(L8)C34 and this binding could be blocked by a gp41 core-specific monoclonal antibody (NC-1). JCH-4, a peptide containing HXXNPF motif, effectively inhibited HIV-1 envelope glycoprotein-mediated syncytium-formation. The epitope of JCH-4 was proven to be linear and might locate in the NHR regions of the gp41 core. These data suggest that HXXNPF motif may be a gp41 core-binding sequence and HXXNPF motif-containing molecules can be used as probes for studying the role of the HIV-1 gp41 core in membrane fusion process.
Huang
Jing-He
JH
Laboratory of Immunology, Department of Biology, Tsinghua University, Protein Science Laboratory of the Ministry of Education, Beijing 100084, PR China.
Liu
Zu-Qiang
ZQ
Liu
Shuwen
S
Jiang
Shibo
S
Chen
Ying-Hua
YH
D016475:3T3 Cells; D020816:Amino Acid Motifs; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D000939:Epitopes; D015700:HIV Envelope Protein gp41 / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008561:Membrane Fusion; D051379:Mice; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D017433:Protein Structure, Secondary
D000911:Antibodies, Monoclonal; D000939:Epitopes; D015700:HIV Envelope Protein gp41; D019151:Peptide Library; D010455:Peptides