Schubert lab: bacterial InIC disrupts human Tuba complexes

How this page was createdHow this page was created

The goal of this page is to provide three-dimensional and interactive figures to explore the structures determined for the 2014 paper "Structural Details of Human Tuba Recruitment by Inlc of Listeria Monocytogenes Elucidate Bacterial Cell-Cell Spreading." by Polle, L., Rigano, L.A., Julian, R., Ireton, K., Schubert, W. published in Structure 22: 304-314.. The starting point are the figures found in this paper [1] . Biochemistry students at Westfield State University recreated these figures in jmol, and revised them after getting feedback from one of the authors, Prof. Wolf-Dieter Schubert [2], University of Pretoria, South Africa. A special thank you goes to Colleen R. Andrews, Kiley D. Baltazar, Caitlyn N. Blanchard, Frederick P. Brincklow, Naomi H. Cosmus, Nicole M. Craig, Albert B. Cuevas, Samantha M. Dominique, Carly Eaton, Courtney A. Finnigan, Kyle S. MacLaughlin, Shelby C. Mader, Vivian Pao, Tia C. Pariseau, Melanie R. Russo, Justin M. Schneider, Michelle G. Thornton, and Sarah J.Ward for making the initial figures and revising them. If you are interested to learn how these figures were created, take a look at the discussion page (2nd tab above).

BackgroundBackground

Listeria monocytogenes is a foodborne pathogen that can infect humans. The infection spreads from cell to cell when bacteria make their way through the junctional membrane. The Listeria protein InIC plays a role as a virulence factor by disrupting protein-protein interactions between the human protein Tuba or Dynamin-binding protein and its binding partners, resulting in a weakening of the actin cytoskeleton and increased success in infecting neighboring cells. The graphical abstract nicely summarizes how protein-protein interactions influence the virulence of Listeria. To get the full story with the benefit of the interactive 3D figures, study the research paper and explore the figures here on proteopedia.

Recreated figuresRecreated figures

[This figure is shown rotating on the right when first viewing the page. To see other figure click on the green links. To get back to this figure (in the original orientation), click on the Figure 1a green link above] Spacefilling representation of the Tuba SH3-6 domain (green) binding to the human N-WASP peptide (red and red dots) and the Mena peptide (yellow). This is a superposition of two separate structures. The SH3 domain binds either peptide, but not at the same time. To see the red dots better, click on +/- quality at the bottom of the 3D browser window. Detail of the interaction showing conserved and non-conserved residues of Tuba making contacts with the N-WASP peptide (red). You can make this figure less busy by turning off the labels (+/- labels switch on the bottom of the 3D browser). You can also look at it as a stereoview (right click under style>stereographic) after opening a pop-up window. InIC Recognition of Tuba SH3-6, with the SH3-6 domain of Tuba in green, the Leucine Rich Repeat domain of InIC in purple and the remainder of InIC in blue. The (translucent) of the proteins takes a while to load but shows the tight contact of the interacting proteins. Details of InIC/Tuba SH3-6 Interaction. F146 of InIC is crucial for the interaction - binding becomes about 100-times weaker when phenylalanine 146 is replaced by alanine (data not shown here, but in the original paper [[1]]). Back to the overall view of . The SH3-6 domain of Tuba (green cartoon) binds both to InIC (cyan and purple cartoon) and to the N-WASP peptide (red spacefilling), but not at the same time. In the figure, the two complexes are superposed, and there are steric clashes (atoms bumping into each other) between InIC's leucine rich repeat (purple) and N-WASP (red). Thus, binding to those two binding partners is mutually exclusive. Surface representation of the Tuba SH3-6 domain, with atoms that contact InIC in blue, atoms that contact N-WASP in pink, and atoms that contact both in the respective complex structures (remember, they can't bind at the same time) in gray. This figure is also available in a , which takes a while to load. (bonus figure) To give you an idea how superpositions work, here are the structures of Tuba-SH3 in complex with N-WASP (green and red) and Tuba-SH3 in complex with MENA (green and yellow). In this figure, the two complexes are far away from each other (they are based on two different experiments, we are just putting them into the same picture). If you click on the "superpose" button below, jmol will overlay carbon alpha atoms of residues 1518-1573 of the SH3 domains as best as possible to minimize the distance between corresponding atoms. The SH3 domain has a slightly different conformation in the two structures, so the best is a superposition with an root mean square deviation (RMSD) of about 0.3 Ångström. The "separate" button will undo the superposition. Be sure to superpose the structures before you go back to other figures (like Fig 1a), otherwise they might look different.

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Other structures associated with the Schubert lab: Schubert, W D