Identification of interaction partners of outer inflammatory protein A: Computational and experimental insights into
Sümeyye Akcelik-Deveci1, Elif Kılıç1, Nesteren Mansur-Ozen1
1Department of Medical Biotechnology, Institute of Health Sciences, Acibadem University, Atasehir, Istanbul, Turkey.
Abstract:
Outer membrane proteins (OMPs) play a key role in facilitating the survival of Helicobacter pylori within the gastric tissue by mediating adherence. Among these proteins, Outer inflammatory protein A (OipA) is a critical factor in H. pylori colonization of the host gastric epithelial cell surface. While the role of OipA in H. pylori attachment and its association with clinical outcomes have been established, the structural mechanisms underlying OipA's action in adherence to gastric epithelial cells remain limited. Our study employed experimental and computational approaches to investigate the interaction partners of OipA on the gastric epithelial cell surface. Initially, we conducted a proteomic analysis using a pull-down assay with recombinant OipA and gastric epithelial cell membrane proteins to identify the OipA interactome. This analysis revealed 704 unique proteins that interacted with OipA. We subsequently analyzed 16 of these OipA partners using molecular modeling tools. Among these 16 partners, we highlight three human proteins, namely Hepatocyte growth factor (HGF), Mesenchymal epithelial transition factor receptor (Met), and Adhesion G Protein-Coupled Receptor B1 (AGRB1) that could play a role in H. pylori adherence to the gastric epithelial cell surface with OipA. Collectively, these findings reveal novel host interactions mediated by OipA, suggesting their potential as therapeutic targets for combating H. pylori infection.
Insights
Outer inflammatory protein A (OipA) from Helicobacter pylori interacts with host cells. This study identifies novel human protein partners, including HGF, Met, and AGRB1, crucial for bacterial adherence and potential therapeutic targets.
Area of Science:
- Microbiology
- Molecular Biology
- Cell Biology
Background:
- Outer membrane proteins (OMPs) are vital for Helicobacter pylori survival in gastric tissue.
- Outer inflammatory protein A (OipA) is essential for H. pylori adherence to gastric epithelial cells.
- The structural mechanisms of OipA's adherence function are not fully understood.
Purpose of the Study:
- To investigate the interaction partners of OipA on the gastric epithelial cell surface.
- To elucidate the structural mechanisms of OipA-mediated adherence.
- To identify potential therapeutic targets for H. pylori infection.
Main Methods:
- Proteomic analysis using pull-down assays with recombinant OipA.
- Identification of the OipA interactome from gastric epithelial cell membrane proteins.
- Molecular modeling of OipA-host protein interactions.
Main Results:
- Proteomic analysis identified 704 unique OipA interacting proteins.
- Molecular modeling analyzed 16 OipA partners.
- Three key human proteins—HGF, Met, and AGRB1—were highlighted for their role in OipA-mediated adherence.
Conclusions:
- OipA engages in novel interactions with host proteins on the gastric epithelial cell surface.
- HGF, Met, and AGRB1 are identified as potential mediators of H. pylori adherence.
- These identified host interactions represent potential therapeutic targets for H. pylori infections.
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