Integrative Computational Analysis Reveals H. pylori GroEL as a Stabilizer of Neurotoxic Amyloid-β Oligomers
Alzheimers disease (AD) is characterized by amyloid-{beta} (A{beta}) aggregation, with soluble oligomers implicated as the most neurotoxic species. Recent evidence suggests microbial infections, including Helicobacter pylori, contribute to AD pathogenesis. This study investigates the role of H. pylori GroEL, a conserved chaperonin found in bacterial outer membrane vesicles (OMVs), in stabilizing toxic A{beta} oligomers. A pan-genome analysis of 353 H. pylori strains identified GroEL as a highly conserved protein present in 83% of strains, which supported its widespread relevance. We structurally modelled a conserved 27-amino acid GroEL fragment and docked it against the A{beta} (1-42) tetramer. Interaction analysis revealed stabilizing salt bridges, hydrogen bonds, and extensive non-bonded contacts within the GroEL-A{beta} complex. Molecular dynamics simulations (50 ns) demonstrated that GroEL binding enhanced A{beta} oligomer stability, evidenced by reduced structural deviations and a more extensive hydrogen bonding network compared to A{beta} oligomer alone. These computational findings support a novel mechanism whereby H. pylori GroEL directly stabilizes soluble A{beta} oligomers. We hypothesize that this stabilization inhibits their aggregation into plaques while paradoxically prolonging the lifetime of neurotoxic species, potentially increasing neurodegeneration through pathways distinct from canonical amyloid deposition. This highlights the complex role of bacterial proteins in AD and underscores the need for experimental validation of GroEL-A{beta} interactions as a potential therapeutic target.