Direct Detection of Membrane-Inserting Fragments Defines the Translocation Pores of a Family of Pathogenic Toxins
| Autor: | Jasmin Lundqvist, Mercedes Di Bernardo, Gunnar von Heijne, Åsa Tellgren-Roth, Kathleen E. Orrell, IngMarie Nilsson, Zhifen Zhang, Roman A. Melnyk, Flavia Cuviello |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Models Molecular Pore Forming Cytotoxic Proteins Protein Conformation Bacterial Toxins Chromosomal translocation Microbiology 03 medical and health sciences Structural Biology Humans Clostridial infection Botulinum Toxins Type A Molecular Biology Biological sciences Microbial toxins 030102 biochemistry & molecular biology Membrane insertion Chemistry Clostridioides difficile Cell Membrane Membrane Proteins Clostridium difficile Protein superfamily 030104 developmental biology Membrane Hydrophobic and Hydrophilic Interactions |
| Zdroj: | Journal of molecular biology. 430(18 Pt) |
| ISSN: | 1089-8638 |
| Popis: | Large clostridial toxins (LCTs) are a family of homologous proteins toxins that are directly responsible for the symptoms associated with a number of clostridial infections that cause disease in humans and in other animals. LCTs damage tissues by delivering a glucosyltransferase domain, which inactivates small GTPases, across the endosomal membrane and into the cytosol of target cells. Elucidating the mechanism of translocation for LCTs has been hampered by difficulties associated with identifying marginally hydrophobic segments that insert into the bounding membrane to form the translocation pore. Here, we directly measured the membrane-insertion partitioning propensity for segments spanning the putative pore-forming region using a translocon-mediated insertion assay and synthetic peptides. We identified membrane-inserting segments, as well as a conserved and functionally important negatively charged residue that requires protonation for efficient membrane insertion. We provide a model of the LCT pore, which provides insights into translocation for this enigmatic family of α-helical translocases. |
| Databáze: | OpenAIRE |
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