Program in Gene Function and Expression
Amino Acid Motifs; Cell Line; HIV-1; Humans; Protein Binding; Protein Interaction Mapping; Ubiquitin; Ubiquitin-Protein Ligases; gag Gene Products, Human Immunodeficiency Virus
Life Sciences | Medicine and Health Sciences
To exit infected cells, human immunodeficiency virus type 1 (HIV-1) exploits the vacuolar protein-sorting pathway by engaging Tsg101 and ALIX through PTAP and LYPx(n)L late assembly (L) domains. In contrast, less-complex retroviruses often use PPxY L domains to recruit Nedd4 family ubiquitin ligases. Although HIV-1 Gag lacks PPxY motifs, we now show that the budding of various HIV-1 L-domain mutants is dramatically enhanced by ectopic Nedd4-2s, a native isoform with a truncated C2 domain. The effect of Nedd4-2s on HIV-1 budding required a catalytically active HECT domain and was specific, since other Nedd4 family proteins showed little activity and an unrelated retrovirus was not rescued. The residual C2 domain of Nedd4-2s was critical for the enhancement of HIV-1 budding and for the association of Nedd4-2s with Gag, as reflected by its incorporation into virus-like particles. Interestingly, the incorporation of Nedd4-2s also depended on its active site, indicating that the ability to form a thioester with ubiquitin was required. These data suggest a novel mechanism by which HIV-1 Gag can connect to cellular budding machinery.
DOI of Published Version
J Virol. 2008 May;82(10):4898-907. Epub 2008 Mar 5. Link to article on publisher's site
Journal of virology
Usami Y, Popov S, Popova E, Gottlinger HG. (2008). Efficient and specific rescue of human immunodeficiency virus type 1 budding defects by a Nedd4-like ubiquitin ligase. Open Access Publications by UMMS Authors. https://doi.org/10.1128/JVI.02675-07. Retrieved from https://escholarship.umassmed.edu/oapubs/2050