title: Structural insights into Ail-mediated adhesion in Yersinia pestis.
abstract: Ail is an outer membrane protein from Yersinia pestis that is highly expressed in a rodent model of bubonic plague, making it a good candidate for vaccine development. Ail is important for attaching to host cells and evading host immune responses, facilitating rapid progression of a plague infection. Binding to host cells is important for injection of cytotoxic Yersinia outer proteins. To learn more about how Ail mediates adhesion, we solved two high-resolution crystal structures of Ail, with no ligand bound and in complex with a heparin analog called sucrose octasulfate. We identified multiple adhesion targets, including laminin and heparin, and showed that a 40 kDa domain of laminin called LG4-5 specifically binds to Ail. We also evaluated the contribution of laminin to delivery of Yops to HEp-2 cells. This work constitutes a structural description of how a bacterial outer membrane protein uses a multivalent approach to bind host cells.
authors.affiliation: Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-8030, USA.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamashita
authors.forename: Petra
authors.initials: P
authors.lastname: Lukacik
authors.forename: Travis J
authors.initials: TJ
authors.lastname: Barnard
authors.forename: Nicholas
authors.initials: N
authors.lastname: Noinaj
authors.forename: Suleyman
authors.initials: S
authors.lastname: Felek
authors.forename: Tiffany M
authors.initials: TM
authors.lastname: Tsang
authors.forename: Eric S
authors.initials: ES
authors.lastname: Krukonis
authors.forename: B Joseph
authors.initials: BJ
authors.lastname: Hinnebusch
authors.forename: Susan K
authors.initials: SK
authors.lastname: Buchanan
mesh_terms: D000595:Amino Acid Sequence; D001422:Bacterial Adhesion; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology; D001426:Bacterial Proteins / Q000378:metabolism; D002460:Cell Line; D018360:Crystallography, X-Ray; D005109:Extracellular Matrix / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D007797:Laminin / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D018832:Molecular Chaperones / Q000378:metabolism; D008969:Molecular Sequence Data; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D013395:Sucrose / Q000031:analogs & derivatives* / Q000737:chemistry; D013499:Surface Properties; D037521:Virulence Factors / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology; D015010:Yersinia pestis
chemical_list: C526543:Ail protein, Yersinia pestis; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D016326:Extracellular Matrix Proteins; D007797:Laminin; D008565:Membrane Proteins; D018832:Molecular Chaperones; D037521:Virulence Factors; C094426:YscG protein, Yersinia; D013395:Sucrose; C053081:sucrose octasulfate
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