Characterization of Vacuolating cytotoxin A binding to sphingomyelin in Helicobacter pylori pathogenesis

Choi, Seokjoo; Hyunjung Anna Kim; Oh, Seung Jin

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https://hdl.handle.net/2142/99954 Copy

Description

Title

Characterization of Vacuolating cytotoxin A binding to sphingomyelin in Helicobacter pylori pathogenesis

Author(s)

• Choi, Seokjoo
• Hyunjung Anna Kim
• Oh, Seung Jin

Contributor(s)

Blanke, Steven R.

Issue Date

2018-04

Keyword(s)

• Helicobacter pylori
• Vacuolating cytotoxin A
• receptor
• sphingomyelin
• toxin

Abstract

The main objective of my research project is to characterize vacuolating cytotoxin A (VacA) from Helicobacter pylori binding to an important host cell membrane lipid, sphingomyelin (SM). Previously, our laboratory showed that plasma membrane SM is important for the toxin biological activity, cell surface binding, and toxin-receptor direct interactions suggesting that SM is a receptor for VacA. Moreover, recent findings from our laboratory showed that R552, W603, and R647 of VacA are important that when changed to alanine, resulting in decreased SM-dependent VacA activity in gastric epithelial cells. However, the molecular basis of SM-VacA interactions remains unknown. My research focuses molecular on the detailed molecular mechanism by which these three residues of VacA interact with SM in SM-dependent toxin cellular activities. I will evaluate the hypothesis that R552, W603, and R647 on VacA facilitate its SM binding by interacting with the phosphorylcholine head group of SM. To test this hypothesis, I will conduct site-directed mutagenesis analysis to evaluate the specific properties of the three residues (R552/W603/R647) that are important for SM-dependent toxin cellular activities. I will evaluate the prediction that VacA interacts with SM through pi-cation interactions between the aromatic ring of tryptophan and choline moiety of head group of SM and ionic interactions between positively charged arginine residues and negatively charged phosphate moiety of SM. Testing this prediction, I am evaluating the toxin cellular activity of charge conservative and non-conservative single substitution mutations in the three residues. The results of this study will provide the framework for the molecular interactions behind VacA-SM interactions.

Type of Resource

image

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http://hdl.handle.net/2142/99954

Copyright and License Information

• Copyright 2018 Seokjoo Choi
• Copyright 2018 Anna Kim Hyunjung
• Copyright 2018 Seung Jin Oh

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