Structural and functional characterization of TlyA hemolysin from Helicobacter pylori
4
Issued Date
2024
Copyright Date
2019
Language
eng
File Type
application/pdf
No. of Pages/File Size
xi, 115 leaves : ill., maps
Access Rights
open access
Rights Holder(s)
Mahidol University
Bibliographic Citation
Thesis (Ph.D. (Immunology))--Mahidol University, 2019
Suggested Citation
Nitchakan Samainukul Structural and functional characterization of TlyA hemolysin from Helicobacter pylori. Thesis (Ph.D. (Immunology))--Mahidol University, 2019. Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/91636
Title
Structural and functional characterization of TlyA hemolysin from Helicobacter pylori
Author(s)
Abstract
Helicobacter pylori gene product HP1086, designated as 'non-conventional' hemolysin named TlyA, is a virulence factor which plays an important role in persistent colonization and disease progression. In this study, 27-kDa TlyA from H. pylori was produced as a soluble recombinant protein in E. coli and purified to near homogeneity by cation exchange chromatography. Purified TlyA was biologically active as proven by membrane-perturbating activity against liposomes in vitro. Quaternary structural assembly and membrane-perturbing activity of TlyA negatively influenced by the addition of reducing agent DTT, thus suggesting a possible function of disulfide bonds for protein activity. Structural model suggests the potential formation of inter-molecular disulfide bridges between Cys124 and Cys128 residues located in the interface within the dimeric assembly. In addition, in silico modeling suggests S-adenosyl methionine (SAM) binding to TlyA could be inhibited by sinefungin which shares the similar binding residues with SAM. Recombinant TlyA causes cytotoxicity in human gastric cells and induces production of cytokine IL-8. Overall, this study disclosed an important role of intermolecular disulfide bonds structural assembly and membrane-perturbing activity of H. pylori TlyA.
Description
Immunology (Mahidol University 2019)
Degree Name
Doctor of Philosophy
Degree Level
Doctoral Degree
Degree Department
Mahidol University. Faculty of Medicine Siriraj Hospital
Degree Discipline
Immunology
Degree Grantor(s)
Mahidol University