Integrase-LEDGF/p75 complex triggers the formation of biomolecular condensates that modulate HIV-1 integration efficiency in vitro.
Fiche publication
Date publication
mai 2024
Journal
The Journal of biological chemistry
Auteurs
Membres identifiés du Cancéropôle Est :
Pr MELY Yves, Dr RUFF Marc, Mr HUMBERT Nicolas
Tous les auteurs :
Batisse C, Lapaillerie D, Humbert N, Real E, Zhu R, Mély Y, Parissi V, Ruff M, Batisse J
Lien Pubmed
Résumé
The pre-integration steps of the HIV-1 viral cycle are some of the most valuable targets of recent therapeutic innovations. HIV-1 integrase (IN) displays multiple functions, thanks to its considerable conformational flexibility. Recently, such flexible proteins have been characterized by their ability to form biomolecular condensates as a result of Liquid-Liquid-Phase-Separation (LLPS), allowing them to evolve in a restricted microenvironment within cells called membrane less organelles (MLO). The LLPS context constitutes a more physiological approach to study the integration molecular mechanisms performed by intasomes (complexes containing viral DNA, IN and its cellular cofactor LEDGF/p75). We investigated here if such complexes can form LLPS in vitro and if IN enzymatic activities were affected by this LLPS environment. We observed that the LLPS formed by IN-LEDGF/p75 functional complexes modulate the in vitro IN activities. While the 3'-processing of viral DNA ends was drastically reduced inside LLPS, viral DNA strand transfer was strongly enhanced. These two catalytic IN activities appear thus tightly regulated by the environment encountered by intasomes.
Mots clés
Integration mechanism regulation, LLPS biomolecular condensates, human immunodeficiency virus, integrase, intrinsically disordered region, macromolecular crowding, viral DNA
Référence
J Biol Chem. 2024 05 16;:107374