title: Effectors of animal and plant pathogens use a common domain to bind host phosphoinositides.
abstract: Bacterial Type III Secretion Systems deliver effectors into host cells to manipulate cellular processes to the advantage of the pathogen. Many host targets of these effectors are found on membranes. Therefore, to identify their targets, effectors often use specialized membrane-localization domains to localize to appropriate host membranes. However, the molecular mechanisms used by many domains are unknown. Here we identify a conserved bacterial phosphoinositide-binding domain (BPD) that is found in functionally diverse Type III effectors of both plant and animal pathogens. We show that members of the BPD family functionally bind phosphoinositides and mediate localization to host membranes. Moreover, NMR studies reveal that the BPD of the newly identified Vibrio parahaemolyticus Type III effector VopR is unfolded in solution, but folds into a specific structure upon binding its ligand phosphatidylinositol-(4,5)-bisphosphate. Thus, our findings suggest a possible mechanism for promoting refolding of Type III effectors after delivery into host cells.
authors.affiliation: Department of Molecular Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9148, USA.
authors.forename: Dor
authors.initials: D
authors.lastname: Salomon
authors.affiliation: Department of Biophysics and Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390-8816, USA.
authors.forename: Yirui
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9050, USA.
authors.forename: Lisa N
authors.initials: LN
authors.lastname: Kinch
authors.affiliation: 1] Department of Biophysics and Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390-8816, USA [2] Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9050, USA.
authors.forename: Nick V
authors.initials: NV
authors.lastname: Grishin
authors.affiliation: Department of Biophysics and Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390-8816, USA.
authors.forename: Kevin H
authors.initials: KH
authors.lastname: Gardner
authors.affiliation: Department of Molecular Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9148, USA.
authors.forename: Kim
authors.initials: K
authors.lastname: Orth
mesh_terms: D016960:Agrobacterium tumefaciens / Q000378:metabolism; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000378:metabolism*; D058947:Bacterial Secretion Systems; D002462:Cell Membrane / Q000378:metabolism; D002736:Chloroplasts / Q000382:microbiology; D004926:Escherichia coli / Q000378:metabolism; D017353:Gene Deletion; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008024:Ligands; D018551:Solanum lycopersicum / Q000382:microbiology; D008565:Membrane Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D010716:Phosphatidylinositols / Q000378:metabolism*; D011485:Protein Binding; D011489:Protein Denaturation; D017434:Protein Structure, Tertiary; D044224:Pseudomonas syringae / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014736:Vibrio parahaemolyticus / Q000378:metabolism; D015011:Yersinia pseudotuberculosis / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D058947:Bacterial Secretion Systems; D008024:Ligands; D008565:Membrane Proteins; D010716:Phosphatidylinositols; D049452:Green Fluorescent Proteins