title: Structural models of intrinsically disordered and calcium-bound folded states of a protein adapted for secretion.
abstract: Many Gram-negative bacteria use Type I secretion systems, T1SS, to secrete virulence factors that contain calcium-binding Repeat-in-ToXin (RTX) motifs. Here, we present structural models of an RTX protein, RD, in both its intrinsically disordered calcium-free Apo-state and its folded calcium-bound Holo-state. Apo-RD behaves as a disordered polymer chain comprising several statistical elements that exhibit local rigidity with residual secondary structure. Holo-RD is a folded multi-domain protein with an anisometric shape. RTX motifs thus appear remarkably adapted to the structural and mechanistic constraints of the secretion process. In the low calcium environment of the bacterial cytosol, Apo-RD is an elongated disordered coil appropriately sized for transport through the narrow secretion machinery. The progressive folding of Holo-RD in the extracellular calcium-rich environment as it emerges form the T1SS may then favor its unidirectional export through the secretory channel. This process is relevant for hundreds of bacterial species producing virulent RTX proteins.
authors.affiliation: Institut Pasteur, UMR CNRS 3528, Chemistry and Structural Biology Department, 75724 PARIS cedex 15, France.
authors.forename: Darragh P
authors.initials: DP
authors.lastname: O'Brien
authors.affiliation: Sorbonne Paris Cité, Université Paris 13, Groupe de Biophysique Moléculaire, UFR Santé-Médecine-Biologie Humaine, 74 rue Marcel Cachin, 93017 Bobigny Cedex, France.
authors.forename: Belen
authors.initials: B
authors.lastname: Hernandez
authors.affiliation: Institut de Biologie Intégrative de la Cellule, UMR 9198, Université Paris-Sud, F-91405 ORSAY Cedex, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Durand
authors.affiliation: Institut Pasteur, UMR CNRS 3528, Chemistry and Structural Biology Department, 75724 PARIS cedex 15, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Hourdel
authors.affiliation: Institut Pasteur, UMR CNRS 3528, Chemistry and Structural Biology Department, 75724 PARIS cedex 15, France.
authors.forename: Ana-Cristina
authors.initials: AC
authors.lastname: Sotomayor-Pérez
authors.affiliation: Institut de Biologie Intégrative de la Cellule, UMR 9198, Université Paris-Sud, F-91405 ORSAY Cedex, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Vachette
authors.affiliation: Sorbonne Paris Cité, Université Paris 13, Groupe de Biophysique Moléculaire, UFR Santé-Médecine-Biologie Humaine, 74 rue Marcel Cachin, 93017 Bobigny Cedex, France.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Ghomi
authors.affiliation: Institut Pasteur, UMR CNRS 3528, Chemistry and Structural Biology Department, 75724 PARIS cedex 15, France.
authors.forename: Julia
authors.initials: J
authors.lastname: Chamot-Rooke
authors.affiliation: Institut Pasteur, UMR CNRS 3528, Chemistry and Structural Biology Department, 75724 PARIS cedex 15, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Ladant
authors.affiliation: Institut Pasteur, UMR CNRS 3528, Chemistry and Structural Biology Department, 75724 PARIS cedex 15, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Brier
authors.affiliation: Institut Pasteur, UMR CNRS 3528, Chemistry and Structural Biology Department, 75724 PARIS cedex 15, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Chenal
mesh_terms: D002118:Calcium / Q000378:metabolism*; D064267:Intrinsically Disordered Proteins / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D054730:Protein Interaction Domains and Motifs; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D064267:Intrinsically Disordered Proteins; D011506:Proteins; D002118:Calcium