title: Helicobacter pylori TlyA Forms Amyloid-like Aggregates with Potent Cytotoxic Activity.
abstract: Helicobacter pylori is a potent human gastric pathogen. It is known to be associated with several gastroenteric disorders, including gastritis, peptic ulcer, and gastric cancer. The H. pylori genome encodes a gene product TlyA that has been shown to display potent membrane damaging properties and cytotoxic activity. On the basis of such properties, TlyA is considered as a potential virulence factor of H. pylori. In this study, we show that the H. pylori TlyA protein has a strong propensity to convert into the amyloid-like aggregated assemblies, upon exposure to elevated temperatures. Even at the physiological temperature of 37 °C, TlyA shows a strong amyloidogenic property. TlyA aggregates that are generated upon exposure at temperatures of ≥37 °C show prominent binding to dyes like thioflavin T and Nile Red. Transmission electron microscopy also demonstrates the presence of typical amyloid-like fibrils in the TlyA aggregates generated at 37 °C. Conversion of TlyA into the amyloid-like aggregates is found to be associated with major alterations in the secondary and tertiary structural organization of the protein. Finally, our study shows that the preformed amyloid-like aggregates of TlyA are capable of exhibiting potent cytotoxic activities against human gastric adenocarcinoma cells. Altogether, such a propensity of H. pylori TlyA to convert into the amyloid-like aggregated assemblies with cytotoxic activity suggests potential implications for the virulence functionality of the protein.
authors.affiliation: Centre for Protein Science, Design and Engineering, Department of Biological Sciences, Indian Institute of Science Education and Research Mohali, Sector 81, S. A. S. Nagar, Manauli 140306, Punjab, India.
authors.forename: Kusum
authors.initials: K
authors.lastname: Lata
authors.affiliation: Centre for Protein Science, Design and Engineering, Department of Biological Sciences, Indian Institute of Science Education and Research Mohali, Sector 81, S. A. S. Nagar, Manauli 140306, Punjab, India.
authors.forename: Kausik
authors.initials: K
authors.lastname: Chattopadhyay
mesh_terms: D000682:Amyloid / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D045744:Cell Line, Tumor; D002470:Cell Survival; D002942:Circular Dichroism; D019295:Computational Biology; D005103:Expert Systems; D005456:Fluorescent Dyes; D005753:Gastric Mucosa / Q000378:metabolism / Q000473:pathology*; D006460:Hemolysin Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D006358:Hot Temperature; D006801:Humans; D046529:Microscopy, Electron, Transmission; D008958:Models, Molecular; D066263:Protein Aggregation, Pathological / Q000378:metabolism / Q000473:pathology; D011487:Protein Conformation; D055550:Protein Stability; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D013050:Spectrometry, Fluorescence; D037521:Virulence Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D000682:Amyloid; D001426:Bacterial Proteins; D005456:Fluorescent Dyes; D006460:Hemolysin Proteins; D011994:Recombinant Proteins; C588092:TlyA protein, Helicobacter pylori; D037521:Virulence Factors