title: Gas-phase conformations of capistruin - comparison of lasso, branched-cyclic and linear topologies.
abstract: BACKGROUND
  Capistruin is a peptide synthesized by Burkholderia thailandensis E264, which displays a lasso topology. This knot-like structure confers interesting properties to peptides (e.g. antibacterial). Therefore, it is important to evaluate the sensitivity of structural characterization methods to such topological constraints.
  
  
  METHODS
  Ion mobility mass spectrometry (IMS-MS) experiments, using both drift tube and travelling wave instruments, were performed on lasso capistruin and on peptides with the same sequence, but displaying a branched-cyclic (un-threaded) or linear topology. Molecular dynamics (MD) simulations were then performed to further interpret the IMS results in terms of conformation.
  
  
  RESULTS
  The collision cross sections (CCSs) measured via IMS for the different forms of capistruin were found to be similar, despite their different topologies for the doubly charged species, but significant differences arise as the charge state is increased. MD simulations for the doubly charged linear peptide were consistent with the hypothesis that salt bridges are present in the gas phase. Moreover, through CCS measurements for peptides with site-specific mutations, the arginine residue at position 11 was found to play a major role in the stabilization of compact structures for the linear peptide.
  
  
  CONCLUSIONS
  Differences in peptide topologies did not yield marked signatures in their respective IMS spectra. Such signatures were only visible for relatively high charge states, that allow Coulomb repulsion to force unfolding. At low charge states, the topologically unconstrained linear form of capistruin was found to adopt charge solvation-constrained structures, possibly including salt bridges, with CCSs comparable to those measured for the topologically constrained lasso form.
authors.affiliation: Normandie Université, COBRA, UMR 6014 and FR 3038, Université de Rouen; INSA Rouen; CNRS, IRCOF, 1 Rue Tesnière, 76821, Mont-Saint-Aignan Cedex, France.
authors.forename: Kevin
authors.initials: K
authors.lastname: Jeanne Dit Fouque
authors.affiliation: Normandie Université, COBRA, UMR 6014 and FR 3038, Université de Rouen; INSA Rouen; CNRS, IRCOF, 1 Rue Tesnière, 76821, Mont-Saint-Aignan Cedex, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Lavanant
authors.affiliation: Molécules de Communication et Adaptation des Microorganismes (MCAM, UMR 7245), Sorbonne Universités, Muséum national d'Histoire naturelle, CNRS, CP 54, 57 rue Cuvier, 75005, Paris, France.
authors.forename: Séverine
authors.initials: S
authors.lastname: Zirah
authors.affiliation: Université de Lyon, Université Lyon 1, ENS Lyon, CNRS UMR5280, ISA, 5 rue de la Doua, 69100, Villeurbanne, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Lemoine
authors.affiliation: Molécules de Communication et Adaptation des Microorganismes (MCAM, UMR 7245), Sorbonne Universités, Muséum national d'Histoire naturelle, CNRS, CP 54, 57 rue Cuvier, 75005, Paris, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Rebuffat
authors.affiliation: Institut Parisien de Chimie Moléculaire, UMR 7201, CNRS, Université Pierre et Marie Curie, 4 place Jussieu, 75005, Paris, France.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Tabet
authors.affiliation: Université de Lyon, Université Lyon 1, CNRS UMR5306, ILM, 5 rue de la Doua, 69100, Villeurbanne, France.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kulesza
authors.affiliation: Normandie Université, COBRA, UMR 6014 and FR 3038, Université de Rouen; INSA Rouen; CNRS, IRCOF, 1 Rue Tesnière, 76821, Mont-Saint-Aignan Cedex, France.
authors.forename: Carlos
authors.initials: C
authors.lastname: Afonso
authors.affiliation: Université de Lyon, Université Lyon 1, CNRS UMR5306, ILM, 5 rue de la Doua, 69100, Villeurbanne, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Dugourd
authors.affiliation: Université de Lyon, Université Lyon 1, ENS Lyon, CNRS UMR5280, ISA, 5 rue de la Doua, 69100, Villeurbanne, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Chirot