title: Structural pierce into molecular mechanism underlying Clostridium perfringens Epsilon toxin function.
abstract: Epsilon toxin of the Clostridium perfringens garnered a lot of attention due to its potential for toxicity in humans, extreme potency for cytotoxicity in mice and lack of any approved therapeutics prescribed for human. However, the intricacies of the Epsilon toxin action mechanism are yet to be understood. In this regard, various in silico tools have been exploited to model and refine the 3D structure of the toxin and its two receptors. The receptor proteins were embedded into designed lipid membranes within an aqueous and ionized environment. Thereafter, the modeled structures subjected to series of consecutive molecular dynamics runs to achieve the most natural like coordination for each model. Ultimately, protein-protein interaction analyses were performed to understand the probable action mechanism. The obtained results successfully confirmed the accuracy of employed methods to achieve high quality models for the toxin and its receptors within their lipid bilayers. Molecular dynamics analyses lead the structures to a more native like coordination. Moreover, the results of previous empirical studies were confirmed, while new insights for action mechanisms including the detailed roles of Hepatitis A virus cellular receptor 1 (HAVCR1) and Myelin and lymphocyte protein (MAL) proteins were achieved. In light of previous and our observations, we suggested novel models which elucidated the existing interplay between potential players of Epsilon toxin action mechanism with detailed structural evidences. These models would pave the way to have more robust understanding of the Epsilon toxin biology, more precise vaccine construction and more successful drug (inhibitor) design.
authors.affiliation: Applied Microbiology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.
authors.forename: Saeed
authors.initials: S
authors.lastname: Khalili
authors.affiliation: Applied Microbiology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.
authors.forename: Abolfazl
authors.initials: A
authors.lastname: Jahangiri
authors.affiliation: Department of Medical Biotechnology, School of Advanced Medical Technologies, Tehran University of Medical Science, Tehran, Iran.
authors.forename: Zahra Sadat
authors.initials: ZS
authors.lastname: Hashemi
authors.affiliation: Poultry Viral Vaccines Research and Production Department, Razi Vaccine and Serum Research Institute, Hesarak, Karaj, Iran.
authors.forename: Bahman
authors.initials: B
authors.lastname: Khalesi
authors.affiliation: Department of Laboratory Sciences, School of Paramedical, Dezful University of Medical Sciences, Dezful, Iran.
authors.forename: Maysam
authors.initials: M
authors.lastname: Mard-Soltani
authors.affiliation: Applied Microbiology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran. Electronic address: jafar.amani@gmail.com.
authors.forename: Jafar
authors.initials: J
authors.lastname: Amani
mesh_terms: D001427:Bacterial Toxins / Q000737:chemistry*; D000072596:Hepatitis A Virus Cellular Receptor 1 / Q000737:chemistry*; D008051:Lipid Bilayers; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D062806:Myelin and Lymphocyte-Associated Proteolipid Proteins / Q000737:chemistry*; D011487:Protein Conformation
chemical_list: D001427:Bacterial Toxins; C039811:Clostridium perfringens epsilon-toxin; D000072596:Hepatitis A Virus Cellular Receptor 1; D008051:Lipid Bilayers; C569028:Mal protein, rat; D062806:Myelin and Lymphocyte-Associated Proteolipid Proteins
keywords: Clostridium perfringens; Epsilon toxin; Molecular dynamics; Protein docking; Structure modeling