Assessment of the interaction of aggregatin protein with amyloid-beta (Aβ) at the molecular level via in silico analysis

Abstract

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 (Aβ)-peptide (1-42) through its N-terminal Aβ binding domain and facilitates Aβ 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 Aβ 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 Aβ. This is the first attempt to demonstrate the interaction of Aggregatin with the Aβ. These results confirmed in vitro and in vivo study reports claiming FAM222A helping to ease the aggregating of the Aβ-peptide.