Surface exposure of the HIV-1 env cytoplasmic tail LLP2 domain during the membrane fusion process: interaction with gp41 fusion core.
HIV-1 gp41 cytoplasmic tail (CT) is highly conserved among HIV-1 isolates, particularly the region designated lentivirus lytic peptide (LLP1-2), which includes two alpha-helical domains LLP1 and LLP2. Although the gp41 CT is recognized as a modulator of viral fusogenicity, little is known about the regulatory mechanism of this region in the viral fusion process. Here we report that anti-LLP1-2 and anti-LLP2 antibodies (IgG) inhibited HIV-1 Env-mediated cell fusion and bound to the interface between effector and target cells at a suboptimal temperature (31.5 degrees C), which slows down the fusion process and prolongs the fusion intermediate state. This suggests that LLP1-2, especially the LLP2 region located inside the viral membrane, is transiently exposed on the membrane surface during the fusion process. Synthetic LLP2 peptide could bind to the gp41 six-helix bundle core with high binding affinity. These results suggest that the gp41 CT may interact with the gp41 core, via the surface-exposed LLP2 domain, to regulate Env-mediated membrane fusion.
Lu
Lu
L
Laboratory of Immunology, Department of Biology, Tsinghua University, Beijing Key Laboratory for Protein Therapeutics, Beijing 100084, China.
Zhu
Yun
Y
Huang
Jinghe
J
Chen
Xi
X
Yang
Hengwen
H
Jiang
Shibo
S
Chen
Ying-Hua
YH
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D002462:Cell Membrane / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D003593:Cytoplasm / Q000378:metabolism*; D015686:Gene Products, env / Q000096:biosynthesis* / Q000737:chemistry; D015700:HIV Envelope Protein gp41 / Q000737:chemistry*; D007074:Immunoglobulin G / Q000737:chemistry; D051379:Mice; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry
D015686:Gene Products, env; D015700:HIV Envelope Protein gp41; D007074:Immunoglobulin G; D011993:Recombinant Fusion Proteins