title: A polar-localized iron-binding protein determines the polar targeting of Burkholderia BimA autotransporter and actin tail formation.
abstract: Intracellular bacterial pathogens including Shigella, Listeria, Mycobacteria, Rickettsia and Burkholderia spp. deploy a specialized surface protein onto one pole of the bacteria to induce filamentous actin tail formation for directional movement within host cytosol. The mechanism underlying polar targeting of the actin tail proteins is unknown. Here we perform a transposon screen in Burkholderia thailandensis and identify a conserved bimC that is required for actin tail formation mediated by BimA from B. thailandensis and its closely related pathogenic species B. pseudomallei and B. mallei. bimC is located upstream of bimA in the same operon. Loss of bimC results in even distribution of BimA on the outer membrane surface, where actin polymerization still occurs. BimC is targeted to the same bacterial pole independently of BimA. BimC confers polar targeting of BimA prior to BimA translocation across bacterial inner membrane. BimC is an iron-binding protein, requiring a four-cysteine cluster at the carboxyl terminus. Mutation of the cysteine cluster disrupts BimC polar localization. Truncation analyses identify the transmembrane domain in BimA being responsible for its polar targeting. Consistently, BimC can interact with BimA transmembrane domain in an iron binding-dependent manner. Our study uncovers a new mechanism that determines the polar distribution of bacteria-induced actin tail in infected host cells.
authors.affiliation: Biological Chemistry, National Institute of Biological Sciences, #7 Science Park Road, Zhongguancun Life Science Park, Beijing, 102206, China.
authors.forename: Qiuhe
authors.initials: Q
authors.lastname: Lu
authors.forename: Yue
authors.initials: Y
authors.lastname: Xu
authors.forename: Qing
authors.initials: Q
authors.lastname: Yao
authors.forename: Miao
authors.initials: M
authors.lastname: Niu
authors.forename: Feng
authors.initials: F
authors.lastname: Shao
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D019117:Burkholderia / Q000235:genetics / Q000378:metabolism*; D004252:DNA Mutational Analysis; D004251:DNA Transposable Elements; D017353:Gene Deletion; D033862:Iron-Binding Proteins / Q000378:metabolism*; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D016254:Mutagenesis, Insertional; D009876:Operon; D011485:Protein Binding; D025941:Protein Interaction Mapping; D021381:Protein Transport
chemical_list: D000199:Actins; D001426:Bacterial Proteins; D004251:DNA Transposable Elements; D033862:Iron-Binding Proteins; D008840:Microfilament Proteins