title: Initial Molecular Recognition Steps of McjA Precursor during Microcin J25 Lasso Peptide Maturation.
abstract: Microcin J25 (MccJ25) has emerged as an excellent model to understand the maturation of ribosomal precursor peptides into the entangled lasso fold. MccJ25 biosynthesis relies on the post-translational modification of the precursor McjA by the ATP-dependent protease McjB and the lactam synthetase McjC. Here, using NMR spectroscopy, we showed that McjA is an intrinsically disordered protein without detectable conformational preference, which emphasizes the active role of the maturation machinery on the three-dimensional folding of MccJ25. We further showed that the N-terminal region of the leader peptide is involved in interaction with both maturation enzymes and identified a predominant interaction of V43-S55 in the core McjA sequence with McjC. Moreover, we demonstrated that residues K23-Q34 in the N-terminal McjA leader peptide tend to adopt a helical conformation in the presence of membrane mimics, implying a role in directing McjA to the membrane in the vicinity of the lasso synthetase/export machinery. These data provide valuable insights into the initial molecular recognition steps in the MccJ25 maturation process.
authors: Institut de Chimie des Substances Naturelles, CNRS UPR 2301, Université Paris-Sud, Université Paris-Saclay, 1 avenue de la Terrasse, 91190, Gif-sur-Yvette, France.
authors: Nadine
authors: N
authors: Assrir
authors: Institut de Chimie des Substances Naturelles, CNRS UPR 2301, Université Paris-Sud, Université Paris-Saclay, 1 avenue de la Terrasse, 91190, Gif-sur-Yvette, France.
authors: Anna
authors: A
authors: Pavelkova
authors: Institut de Chimie des Substances Naturelles, CNRS UPR 2301, Université Paris-Sud, Université Paris-Saclay, 1 avenue de la Terrasse, 91190, Gif-sur-Yvette, France.
authors: Régine
authors: R
authors: Dazzoni
authors: Molécules de Communication et Adaptation des Microorganismes, UMR 7245 CNRS, Muséum National d'Histoire Naturelle, Sorbonne Universités, CP 54, 57 rue Cuvier, 75005, Paris, France.
authors: Rémi
authors: R
authors: Ducasse
authors: Institut de Chimie des Substances Naturelles, CNRS UPR 2301, Université Paris-Sud, Université Paris-Saclay, 1 avenue de la Terrasse, 91190, Gif-sur-Yvette, France.
authors: Nelly
authors: N
authors: Morellet
authors: Institut de Chimie des Substances Naturelles, CNRS UPR 2301, Université Paris-Sud, Université Paris-Saclay, 1 avenue de la Terrasse, 91190, Gif-sur-Yvette, France.
authors: Eric
authors: E
authors: Guittet
authors: Molécules de Communication et Adaptation des Microorganismes, UMR 7245 CNRS, Muséum National d'Histoire Naturelle, Sorbonne Universités, CP 54, 57 rue Cuvier, 75005, Paris, France.
authors: Sylvie
authors: S
authors: Rebuffat
authors: Molécules de Communication et Adaptation des Microorganismes, UMR 7245 CNRS, Muséum National d'Histoire Naturelle, Sorbonne Universités, CP 54, 57 rue Cuvier, 75005, Paris, France.
authors: Séverine
authors: S
authors: Zirah
authors: Molécules de Communication et Adaptation des Microorganismes, UMR 7245 CNRS, Muséum National d'Histoire Naturelle, Sorbonne Universités, CP 54, 57 rue Cuvier, 75005, Paris, France.
authors: Yanyan
authors: Y
authors: Li
authors: Institut de Chimie des Substances Naturelles, CNRS UPR 2301, Université Paris-Sud, Université Paris-Saclay, 1 avenue de la Terrasse, 91190, Gif-sur-Yvette, France. ewen.lescop@cnrs.fr.
authors: Ewen
authors: E
authors: Lescop
mesh_terms: D001430:Bacteriocins / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D017510:Protein Folding
chemical_list: D001430:Bacteriocins; D010455:Peptides; C020411:microcin
keywords: NMR spectroscopy; SDS micelles; biosynthesis; intrinsically disordered protein; lasso peptide