Luisa F. Jimenez

Publications (10) View all

• Source

  Available from: Laurent Terradot

  Article: Structural insights into Helicobacter pylori oncoprotein CagA interaction with β1 integrin.

  Burcu Kaplan-Türköz, Luisa F Jiménez-Soto, Cyril Dian, Claudia Ertl, Han Remaut, Arthur Louche, Tommaso Tosi, Rainer Haas, Laurent Terradot
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  ABSTRACT: Infection with the gastric pathogen Helicobacter pylori is a risk factor for the development of gastric cancer. Pathogenic strains of H. pylori carry a type IV secretion system (T4SS) responsible for the injection of the oncoprotein CagA into host cells. H. pylori and its cag-T4SS exploit α5β1 integrin as a receptor for CagA translocation. Injected CagA localizes to the inner leaflet of the host cell membrane, where it hijacks host cell signaling and induces cytoskeleton reorganization. Here we describe the crystal structure of the N-terminal ∼100-kDa subdomain of CagA at 3.6 Å that unveils a unique combination of folds. The core domain of the protein consists of an extended single-layer β-sheet stabilized by two independent helical subdomains. The core is followed by a long helix that forms a four-helix helical bundle with the C-terminal domain. Mapping of conserved regions in a set of CagA sequences identified four conserved surface-exposed patches (CSP1-4), which represent putative hot-spots for protein-protein interactions. The proximal part of the single-layer β-sheet, covering CSP4, is involved in specific binding of CagA to the β1 integrin, as determined by yeast two-hybrid and in vivo competition assays in H. pylori cell-culture infection studies. These data provide a structural basis for the first step of CagA internalization into host cells and suggest that CagA uses a previously undescribed mechanism to bind β1 integrin to mediate its own translocation.
  Proceedings of the National Academy of Sciences 08/2012; 109(36):14640-5. · 9.68 Impact Factor
• Article: Retroviruses can establish filopodial bridges for efficient cell-to-cell transmission.

  Nathan M Sherer, Maik J Lehmann, Luisa F Jimenez-Soto, Christina Horensavitz, Marc Pypaert, Walther Mothes
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  ABSTRACT: The spread of retroviruses between cells is estimated to be 2-3 orders of magnitude more efficient when cells can physically interact with each other. The underlying mechanism is largely unknown, but transfer is believed to occur through large-surface interfaces, called virological or infectious synapses. Here, we report the direct visualization of cell-to-cell transmission of retroviruses in living cells. Our results reveal a mechanism of virus transport from infected to non-infected cells, involving thin filopodial bridges. These filopodia originate from non-infected cells and interact, through their tips, with infected cells. A strong association of the viral envelope glycoprotein (Env) in an infected cell with the receptor molecules in a target cell generates a stable bridge. Viruses then move along the outer surface of the filopodial bridge toward the target cell. Our data suggest that retroviruses spread by exploiting an inherent ability of filopodia to transport ligands from cell to cell.
  Nature Cell Biology 04/2007; 9(3):310-5. · 19.49 Impact Factor
• Source

  Available from: Luisa F. Jimenez

  Article: Visualization of retroviral replication in living cells reveals budding into multivesicular bodies.

  Nathan M Sherer, Maik J Lehmann, Luisa F Jimenez-Soto, Alyssa Ingmundson, Stacy M Horner, Gregor Cicchetti, Philip G Allen, Marc Pypaert, James M Cunningham, Walther Mothes
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  ABSTRACT: Retroviral assembly and budding is driven by the Gag polyprotein and requires the host-derived vacuolar protein sorting (vps) machinery. With the exception of human immunodeficiency virus (HIV)-infected macrophages, current models predict that the vps machinery is recruited by Gag to viral budding sites at the cell surface. However, here we demonstrate that HIV Gag and murine leukemia virus (MLV) Gag also drive assembly intracellularly in cell types including 293 and HeLa cells, previously believed to exclusively support budding from the plasma membrane. Using live confocal microscopy in conjunction with electron microscopy of cells generating fluorescently labeled virions or virus-like particles, we observed that these retroviruses utilize late endosomal membranes/multivesicular bodies as assembly sites, implying an endosome-based pathway for viral egress. These data suggest that retroviruses can interact with the vps sorting machinery in a more traditional sense, directly linked to the mechanism by which cellular proteins are sorted into multivesicular endosomes.
  Traffic 12/2003; 4(11):785-801. · 4.92 Impact Factor
• Source

  Available from: Luisa F. Jimenez

  Article: CagI is an essential component of the Helicobacter pylori Cag type IV secretion system and forms a complex with CagL.

  Kieu Thuy Pham, Evelyn Weiss, Luisa F Jiménez Soto, Ute Breithaupt, Rainer Haas, Wolfgang Fischer
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  ABSTRACT: Helicobacter pylori, the causative agent of type B gastritis, peptic ulcers, gastric adenocarcinoma and MALT lymphoma, uses the Cag type IV secretion system to induce a strong proinflammatory response in the gastric mucosa and to inject its effector protein CagA into gastric cells. CagA translocation results in altered host cell gene expression profiles and cytoskeletal rearrangements, and it is considered as a major bacterial virulence trait. Recently, it has been shown that binding of the type IV secretion apparatus to integrin receptors on target cells is a crucial step in the translocation process. Several bacterial proteins, including the Cag-specific components CagL and CagI, have been involved in this interaction. Here, we have examined the localization and interactions of CagI in the bacterial cell. Since the cagI gene overlaps and is co-transcribed with the cagL gene, the role of CagI for type IV secretion system function has been difficult to assess, and conflicting results have been reported regarding its involvement in the proinflammatory response. Using a marker-free gene deletion approach and genetic complementation, we show now that CagI is an essential component of the Cag type IV secretion apparatus for both CagA translocation and interleukin-8 induction. CagI is distributed over soluble and membrane-associated pools and seems to be partly surface-exposed. Deletion of several genes encoding essential Cag components has an impact on protein levels of CagI and CagL, suggesting that both proteins require partial assembly of the secretion apparatus. Finally, we show by co-immunoprecipitation that CagI and CagL interact with each other. Taken together, our results indicate that CagI and CagL form a functional complex which is formed at a late stage of secretion apparatus assembly.
  PLoS ONE 01/2012; 7(4):e35341. · 4.09 Impact Factor
• Source

  Available from: uni-muenchen.de

  Article: Studies on the function of the Cag Type IV Secretion System of Helicobacter pylori with integrin Beta1

  Luisa Fernanda Jimenez Soto