Bioinformatic Analysis of the PRNP Gene

The PRNP gene encodes a lipid-anchored protein localized to the outer surface of cell membranes. The exact function of the protein (PrP^c) coded by this gene is not fully understood, but it may mediate neuron homeostasis, cell signaling, and brain tissue response to oxidative stress experienced during strokes. Mutations in the PRNP gene have been implicated in neurodegenerative diseases where a misfolded variant of the protein, incapable of being degraded by cells, aggregates within the brain and leads to the formation of tiny holes resulting in rapid onset dementia and death. The protein consists of distinct parts with unique biochemical and structural characteristics. A flexible, unstructured region projects outward from the cell, while a more structured region remains anchored closer to the cell membrane. The protein can be cleaved at specific residues with the resulting fragments influencing the immediate neuronal microenvironment. Mutated isoforms of the PrP protein are routinely called prions and can induce properly folded PrP proteins to misfold and aggregate due to the hydrophobic effect and other intermolecular interactions.  The current study examines a mutation of the PRNP gene and analyzes the molecular consequences upon protein structure. Computational analysis of this mutated protein will generate significant data, elucidating some of the forces governing the protein’s folding while also helping to predict pathologies. The relevance of this study is underscored by the fact that a protein’s three-dimensional structure directly impacts its function, and misfolded proteins are involved in cellular aging and diseases such as Alzheimer's, type 2 diabetes mellitus, Tay Sach’s, and Creutzfeldt-Jakob disease.