title: Autotransporter passenger domain secretion requires a hydrophobic cavity at the extracellular entrance of the β-domain pore.
abstract: Whooping cough (pertussis) is a highly contagious acute respiratory illness of humans caused by the Gram-negative bacterial pathogen Bordetella pertussis. The AT (autotransporter) BrkA (Bordetella serum-resistance killing protein A) is an important B. pertussis virulence factor that confers serum resistance and mediates adherence. In the present study, we have solved the crystal structure of the BrkA β-domain at 3 Å (1 Å=0.1 nm) resolution. Special features are a hairpin-like structure formed by the external loop L4, which is observed fortuitously sitting inside the pore of the crystallographic adjacent β-domain, and a previously undiscovered hydrophobic cavity formed by patches on loop L4 and β-strands S5 and S6. This adopts a ubiquitous structure characteristic of all AT β-domains. Mutagenesis studies have demonstrated that the hairpin-like structure and hydrophobic cavity are crucial for BrkA passenger domain (virulence effector) translocation. This structure helps in understanding the molecular mechanism of AT assembly and secretion and provides a potential target for anti-pertussis drug design.
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Yujia
authors.initials: Y
authors.lastname: Zhai
authors.forename: Kai
authors.initials: K
authors.lastname: Zhang
authors.forename: Yanwu
authors.initials: Y
authors.lastname: Huo
authors.forename: Yanshi
authors.initials: Y
authors.lastname: Zhu
authors.forename: Qiangjun
authors.initials: Q
authors.lastname: Zhou
authors.forename: Jiuwei
authors.initials: J
authors.lastname: Lu
authors.forename: Isobel
authors.initials: I
authors.lastname: Black
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Pang
authors.forename: Aleksander W
authors.initials: AW
authors.lastname: Roszak
authors.forename: Xujia
authors.initials: X
authors.lastname: Zhang
authors.forename: Neil W
authors.initials: NW
authors.lastname: Isaacs
authors.forename: Fei
authors.initials: F
authors.lastname: Sun
mesh_terms: D000595:Amino Acid Sequence; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D001886:Bordetella pertussis / Q000235:genetics / Q000378:metabolism*; D004269:DNA, Bacterial / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D021381:Protein Transport
chemical_list: D001425:Bacterial Outer Membrane Proteins; C090007:BrkA protein, Bordetella pertussis; D004269:DNA, Bacterial