Special Issue "Intracellular Traffic and Transport of Bacterial Protein Toxins"
Deadline for manuscript submissions: 31 May 2014
Prof. Dr. Holger Barth
Institut für Pharmakologie und Toxikologie, Universitätsklinikum Ulm, Albert-Einstein-Allee 11, 89081 Ulm, Germany
Phone: +49 731 50065503
Fax: +49 731 50065502
Interests: bacterial protein toxins; actin; Rho-GTPases; macrophages; cellular uptake and intracellular membrane transport of bacterial toxins; interaction of bacterial toxins with host cell chaperones; bacterial toxins as Molecular Trojan Horses for drug delivery
Bacterial protein toxins which act as enzymes in the cytosol of mammalian cells are the causative agents for a variety of severe human and animals diseases. Significant progress was made in understanding the cellular uptake, the intracellular traffic of bacterial toxins and their interaction with host cell factors including chaperones and folding helper enzymes during transport of their enzymatic active subunits across intracellular membranes into the host cell cytosol. However, for many toxins their cellular receptors as well as the detailed molecular mechanisms underlying their membrane translocation are still not known. Since uptake into the cytosol of target cells is essential for the cytotoxic mode of action of most medically relevant toxins, a targeted pharmacological inhibition of toxin uptake into cells could result in novel therapeutic strategies against toxin-associated diseases. On the other hand, non-toxic portions of bacterial toxins can serve as "Molecular Trojan Horses" for efficient delivery of therapeutic molecules into target cells.
This special issue of Toxins covers new findings about the intracellular traffic and transport of bacterial protein toxins as well as their pharmacological exploitations.
Prof. Dr. Holger Barth
Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.
Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Toxins is an international peer-reviewed Open Access monthly journal published by MDPI.
- bacterial protein toxins
- cellular uptake
- intracellular traffic
- membrane transport
- role of host cell factors in toxin translocation
- pharmacological strategies to inhibit toxin uptake into cells
The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.
Authors: Alexandre Chenal
Affiliation: Biochemistry of Macromolecular Interactions Unit Chemistry and Structural Biology Department UMR CNRS 3528 – Structural Biology& Infectious Agents BioTop 4th floor, room 16 INSTITUT PASTEUR 25-28, rue du Dr Roux 75724 Paris cedex 15 France
Abstract: Ligand-induced disorder-to-order transition plays a key role in the biological functions of many proteins that contain intrinsically disordered domains. Here, we review data on an RTX (« Repeat in ToXin ») protein, RCL, an IDP that folds upon calcium binding. RTX motifs are calcium-binding nonapeptide sequences that are found in more than 250 virulence factors secreted by Gram-negative pathogenic bacteria. Using a combination of biophysical approaches, we showed that RCL exhibits the hallmarks of intrinsically disordered proteins in the absence of calcium. Calcium binding triggers a strong reduction of the mean net charge, dehydration and compaction, folding and stabilization of secondary and tertiary structures of RCL. Altogether, our data suggest that, in the apo-state as found in the crowded bacterial cytosol, RTX proteins adopt extended unfolded conformations that may facilitate protein export by the secretion machinery. Subsequently, calcium gradient across bacterial cell wall and crowding also enhances the calcium-dependent folding and stability of RTX proteins once secreted in the extracellular milieu.
Last update: 31 March 2014