title: Context-dependent protein folding of a virulence peptide in the bacterial and host environments: structure of an SycH-YopH chaperone-effector complex.
abstract: Yersinia pestis injects numerous bacterial proteins into host cells through an organic nanomachine called the type 3 secretion system. One such substrate is the tyrosine phosphatase YopH, which requires an interaction with a cognate chaperone in order to be effectively injected. Here, the first crystal structure of a SycH-YopH complex is reported, determined to 1.9 Å resolution. The structure reveals the presence of (i) a nonglobular polypeptide in YopH, (ii) a so-called β-motif in YopH and (iii) a conserved hydrophobic patch in SycH that recognizes the β-motif. Biochemical studies establish that the β-motif is critical to the stability of this complex. Finally, since previous work has shown that the N-terminal portion of YopH adopts a globular fold that is functional in the host cell, aspects of how this polypeptide adopts radically different folds in the host and in the bacterial environments are analysed.
authors.affiliation: Laboratory of Structural Microbiology, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Milos
authors.initials: M
authors.lastname: Vujanac
authors.forename: C Erec
authors.initials: CE
authors.lastname: Stebbins
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry*; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D018360:Crystallography, X-Ray; D054884:Host-Pathogen Interactions; D018832:Molecular Chaperones / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D017510:Protein Folding; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry*; D037521:Virulence Factors / Q000737:chemistry* / Q000378:metabolism; D015010:Yersinia pestis / Q000737:chemistry
chemical_list: D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D018832:Molecular Chaperones; D010455:Peptides; C090049:SycH protein, Yersinia; D037521:Virulence Factors; D017027:Protein Tyrosine Phosphatases; C067571:yopH protein, Yersinia
keywords: SycH; Yersinia pestis; YopH; bacterial pathogenesis; chaperones; type 3 secretion; virulence peptides