title: Structure and plasticity of the peptidyl-prolyl isomerase Par27 of Bordetella pertussis revealed by X-ray diffraction and small-angle X-ray scattering.
abstract: Par27 from Bordetella pertussis belongs to a newly discovered class of dimeric peptidyl-prolyl isomerase (PPIase)/chaperones from the parvulin family. It is a tripartite protein with a central PPIase domain surrounded by N- and C-terminal sub-domains (NTD and CTD). Here, the Par27 structure was characterized by X-ray crystallography, small-angle X-ray scattering and template-based modeling. In the crystal lattice, Par27 consists of alternating well ordered and poorly ordered domains. The PPIase domains gave rise to diffuse scattering and could not be solved, whereas a 2.2A resolution crystal structure was obtained for the NTD and CTD, revealing a cradle-shaped dimeric platform. Despite a lack of sequence similarity with corresponding sub-domains, the topology of the peptide chain in the NTD/CTD core is similar to that of other monomeric PPIase/chaperones such as SurA and trigger factor from Escherichia coli. In Par27, dimerization occurs by sub-domain swapping. Because of the strong amino acid sequence similarity to other parvulin domains, a model for the Par27 PPIase domain was built by template-based modeling and validated against small-angle X-ray scattering (SAXS) data. A model of the full-length dimeric Par27 structure was built by rigid-body modeling and filtering against SAXS data using the partial crystal structure of the NTD/CTD core and the template-based PPIase model. The flexibility of protein was accounted for by representing the structure as an ensemble of different conformations that collectively reproduce the scattering data. The refined models exhibit a cradle-like shape reminiscent of other PPIase/chaperones, and the variability in the orientation of the PPIase domains relative to the NTD/CTD core platform observed in the different models suggests inter-domain flexibility that could be important for the biological activity of this protein.
authors.affiliation: UMR8161 CNRS, Institut de Biologie de Lille, Institut Pasteur de Lille, Université de Lille 1 - Université de Lille 2, 1 rue Calmette, 59021 Lille Cedex, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Clantin
authors.forename: Cédric
authors.initials: C
authors.lastname: Leyrat
authors.forename: Alex
authors.initials: A
authors.lastname: Wohlkönig
authors.forename: Hélène
authors.initials: H
authors.lastname: Hodak
authors.forename: Euripedes de Almeida
authors.initials: Ede A
authors.lastname: Ribeiro
authors.forename: Nicolas
authors.initials: N
authors.lastname: Martinez
authors.forename: Catherine
authors.initials: C
authors.lastname: Baud
authors.forename: Caroline
authors.initials: C
authors.lastname: Smet-Nocca
authors.forename: Vincent
authors.initials: V
authors.lastname: Villeret
authors.forename: Françoise
authors.initials: F
authors.lastname: Jacob-Dubuisson
authors.forename: Marc
authors.initials: M
authors.lastname: Jamin
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001886:Bordetella pertussis / Q000201:enzymology*; D056004:Molecular Dynamics Simulation; D019696:Peptidylprolyl Isomerase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D053838:Scattering, Small Angle; D014961:X-Ray Diffraction
chemical_list: D001426:Bacterial Proteins; D011994:Recombinant Proteins; D019696:Peptidylprolyl Isomerase