title: Structural and Functional Investigations of the Effector Protein LpiR1 from Legionella pneumophila.
abstract: Legionella pneumophila is a causative agent of a severe pneumonia, known as Legionnaires' disease. Legionella pathogenicity is mediated by specific virulence factors, called bacterial effectors, which are injected into the invaded host cell by the bacterial type IV secretion system. Bacterial effectors are involved in complex interactions with the components of the host cell immune and signaling pathways, which eventually lead to bacterial survival and replication inside the mammalian cell. Structural and functional studies of bacterial effectors are, therefore, crucial for elucidating the mechanisms of Legionella virulence. Here we describe the crystal structure of the LpiR1 (Lpg0634) effector protein and investigate the effects of its overexpression in mammalian cells. LpiR1 is an α-helical protein that consists of two similar domains aligned in an antiparallel fashion. The hydrophilic cleft between the domains might serve as a binding site for a potential host cell interaction partner. LpiR1 binds the phosphate group at a conserved site and is stabilized by Mn(2+), Ca(2+), or Mg(2+) ions. When overexpressed in mammalian cells, a GFP-LpiR1 fusion protein is localized in the cytoplasm. Intracellular signaling antibody array analysis revealed small changes in the phosphorylation state of several components of the Akt signaling pathway in HEK293T cells overexpressing LpiR1.
authors.affiliation: From the Department of Biochemistry and.
authors.forename: Ksenia A
authors.initials: KA
authors.lastname: Beyrakhova
authors.affiliation: From the Department of Biochemistry and.
authors.forename: Karin
authors.initials: K
authors.lastname: van Straaten
authors.affiliation: From the Department of Biochemistry and.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.affiliation: From the Department of Biochemistry and.
authors.forename: Michal T
authors.initials: MT
authors.lastname: Boniecki
authors.affiliation: Cancer Research, Saskatchewan Cancer Agency, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5E5, Canada.
authors.forename: Deborah H
authors.initials: DH
authors.lastname: Anderson
authors.affiliation: From the Department of Biochemistry and miroslaw.cygler@usask.ca.
authors.forename: Miroslaw
authors.initials: M
authors.lastname: Cygler
mesh_terms: D058947:Bacterial Secretion Systems / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D016952:Legionella pneumophila / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity; D007877:Legionnaires' Disease / Q000235:genetics / Q000378:metabolism; D008670:Metals / Q000737:chemistry / Q000378:metabolism; D000072417:Protein Domains; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D037521:Virulence Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D058947:Bacterial Secretion Systems; D008670:Metals; D037521:Virulence Factors; D051057:Proto-Oncogene Proteins c-akt
keywords: Legionella infection; bacterial pathogenesis; cell signaling; cellular localization; crystal structure; protein evolution; protein-protein interaction