Efficient trapping of HIV-1 envelope protein by hetero-oligomerization with an N-helix chimera.
BACKGROUND
The N-heptad repeat region of the HIV-1 Transmembrane Envelope protein is a trimerization domain that forms part of a "six helix bundle" crucial to Envelope-mediated membrane fusion. N-heptad repeat peptides have been used as extracellular reagents to inhibit virus fusion.


RESULTS
When expressed intracellularly with wild-type HIV-1 Envelope protein, the N-heptad repeat domain efficiently hetero-oligomerized with Envelope and trapped it in the endoplasmic reticulum or early Golgi, as indicated by lack of transport to the cell surface, absent proteolytic processing, and aberrant glycosylation.


CONCLUSIONS
Post-translational processing of HIV Envelope is very sensitive to an agent that binds to the N-heptad repeat during synthesis, suggesting that it might be possible to modify drugs that bind to this region to have transport-blocking properties.
Ou
Wu
W
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 4, Bethesda, MD 20892, USA. wou@niaid.nih.gov
Silver
Jonathan
J
D019380:Anti-HIV Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000737:chemistry; D019921:Biotinylation; D004721:Endoplasmic Reticulum / Q000378:metabolism; D015686:Gene Products, env / Q000737:chemistry* / Q000502:physiology; D015497:HIV-1 / Q000737:chemistry / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D008164:Luminescent Proteins / Q000737:chemistry; D008561:Membrane Fusion; D011499:Protein Processing, Post-Translational; D017433:Protein Structure, Secondary; D021381:Protein Transport; D019713:Receptors, CCR5 / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D020449:Repetitive Sequences, Amino Acid
D019380:Anti-HIV Agents; D001426:Bacterial Proteins; D015686:Gene Products, env; D008164:Luminescent Proteins; D019713:Receptors, CCR5; D011993:Recombinant Fusion Proteins; C054562:yellow fluorescent protein, Bacteria