The nucleic acid chaperone activity of the HIV-1 Gag polyprotein is boosted by its cellular partner RPL7: a kinetic study. Issue 16 (14th August 2020)

• Record Type: Journal Article
• Authors: Karnib, Hassan; Nadeem, Muhammad F; Humbert, Nicolas; Sharma, Kamal K; Grytsyk, Natalia; Tisné, Carine; Boutant, Emmanuel; Lequeu, Thiebault; Réal, Eleonore; Boudier, Christian; de Rocquigny, Hugues; Mély, Yves
• Is Part Of: Nucleic acids research. Volume 48:Issue 16(2020)
• Page Start: 9218
• Page End: 9234
• Publication Date: 2020-08-14
• Subjects: Nucleic acids -- Periodicals; Molecular biology -- Periodicals; 572.805
• DOI: 10.1093/nar/gkaa659
• Languages: English
• ISSNs: 0305-1048

Abstract

Abstract: The HIV-1 Gag protein playing a key role in HIV-1 viral assembly has recently been shown to interact through its nucleocapsid domain with the ribosomal protein L7 (RPL7) that acts as a cellular co-factor promoting Gag's nucleic acid (NA) chaperone activity. To further understand how the two proteins act together, we examined their mechanism individually and in concert to promote the annealing between dTAR, the DNA version of the viral transactivation element and its complementary cTAR sequence, taken as model HIV-1 sequences. Gag alone or complexed with RPL7 was found to act as a NA chaperone that destabilizes cTAR stem-loop and promotes its annealing with dTAR through the stem ends via a two-step pathway. In contrast, RPL7 alone acts as a NA annealer that through its NA aggregating properties promotes cTAR/dTAR annealing via two parallel pathways. Remarkably, in contrast to the isolated proteins, their complex promoted efficiently the annealing of cTAR with highly stable dTAR mutants. This was confirmed by the RPL7-promoted boost of the physiologically relevant Gag-chaperoned annealing of (+)PBS RNA to the highly stable tRNA Lys 3 primer, favoring the notion that Gag recruits RPL7 to overcome major roadblocks in viral assembly.