Investigation of the Low-Populated Excited States of the HIV-1 Nucleocapsid Domain
Assia Mouhand,
Loussiné Zargarian,
Anissa Belfetmi,
Marjorie Catala,
Marco Pasi,
Ewen Lescop,
Carine Tisné,
Olivier Mauffret
Affiliations
Assia Mouhand
Expression Génétique Microbienne, UMR 8261, CNRS, Institut de Biologie Physico-Chimique (IBPC), Université de Paris, 75005 Paris, France
Loussiné Zargarian
Laboratoire de Biologie et de Pharmacologie Appliquée (LBPA), UMR 8113 CNRS, Institut D’Alembert, École Normale Supérieure Paris-Saclay, Université Paris-Saclay, 4, Avenue des Sciences, 91190 Gif sur Yvette, France
Anissa Belfetmi
Laboratoire de Biologie et de Pharmacologie Appliquée (LBPA), UMR 8113 CNRS, Institut D’Alembert, École Normale Supérieure Paris-Saclay, Université Paris-Saclay, 4, Avenue des Sciences, 91190 Gif sur Yvette, France
Marjorie Catala
Expression Génétique Microbienne, UMR 8261, CNRS, Institut de Biologie Physico-Chimique (IBPC), Université de Paris, 75005 Paris, France
Marco Pasi
Laboratoire de Biologie et de Pharmacologie Appliquée (LBPA), UMR 8113 CNRS, Institut D’Alembert, École Normale Supérieure Paris-Saclay, Université Paris-Saclay, 4, Avenue des Sciences, 91190 Gif sur Yvette, France
Ewen Lescop
Institut de Chimie des Substances Naturelles, UPR2301 CNRS, Université Paris-Saclay, 1 av. de la Terrasse, 91198 Gif-sur-Yvette, France
Carine Tisné
Expression Génétique Microbienne, UMR 8261, CNRS, Institut de Biologie Physico-Chimique (IBPC), Université de Paris, 75005 Paris, France
Olivier Mauffret
Laboratoire de Biologie et de Pharmacologie Appliquée (LBPA), UMR 8113 CNRS, Institut D’Alembert, École Normale Supérieure Paris-Saclay, Université Paris-Saclay, 4, Avenue des Sciences, 91190 Gif sur Yvette, France
The nucleocapsid domain (NCd), located at the C-terminus of the HIV-1 Gag protein, is involved in numerous stages of the replication cycle, such as the packaging of the viral genome and reverse transcription. It exists under different forms through the viral life cycle, depending on the processing of Gag by the HIV-1 protease. NCd is constituted of two adjacent zinc knuckles (ZK1 and ZK2), separated by a flexible linker and flanked by disordered regions. Here, conformational equilibria between a major and two minor states were highlighted exclusively in ZK2, by using CPMG and CEST NMR experiments. These minor states appear to be temperature dependent, and their populations are highest at physiological temperature. These minor states are present both in NCp7, the mature form of NCd, and in NCp9 and NCp15, the precursor forms of NCd, with increased populations. The role of these minor states in the targeting of NCd by drugs and its binding properties is discussed.
