Assessment of the Interaction of Aggregatin Protein with Amyloid-Beta (Aβ) at the Molecular Level via In Silico Analysis.

Alzheimer's disease is a major neurodegenerative illness whose prevalence is increasing worldwide but the molecular mechanism remains unclear. There is some scientific evidence that the molecular complexity of Alzheimer's pathophysiology is associated with the formation of extracellular amyloid-beta plaques in the brain. A novel cross-phenotype association analysis of imaging genetics reported a brain atrophy susceptibility gene, namely FAM222A and the protein Aggregatin encoded by FAM222A interacts with amyloid-beta (Aß)-peptide (1-42) through its N-terminal Aß binding domain and facilitates Aß aggregation. The function of Aggregatin protein is unknown, and its three-dimensional structure has not been analyzed experimentally yet. Our goal was to investigate the interaction of Aggregatin with Aß in detail by in silico analysis, including the 3D structure prediction analysis of Aggregatin protein by homology modeling. Our analysis verified the interaction of the C-terminal domain of model protein with the N-terminal domain of Aß. This is the first attempt to demonstrate the interaction of Aggregatin with the Aß. These results confirmed in vitro and in vivo study reports claiming FAM222A helping to ease the aggregating of the Aß-peptide. [ABSTRACT FROM AUTHOR]