Testing the ability of RF-amide neuropeptides to promote amyloidosis of recombinant human prion protein
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Protein folding is a process in which polypeptides assume their correct conformational tertiary structure from a random coil to produce a functional protein. When the protein does not fold correctly, complications can occur that can cause major problems. This process is known as protein misfolding and is observed in amyloid related diseases. Progression of protein misfolding often involves the structural conversion of normal cellular protein into amyloid oligomers rich in β-sheet structure. These oligomers form plaques of insoluble fibrils that accumulate in tissues and organs, causing cytotoxicity and are detrimental to neuronal cells. The conformational changes in protein structure that are associated with protein misfolding can occur through binding interactions with other molecules. Previously, it was shown that a small peptide ligand containing the sequence lysine-phenylalanine- alanine-lysine-phenylalanine (KFAKF) could promote amyloid conversion of recombinant purified human prion protein (hPrP) under physiological-like conditions. Of note, the sequence of this small peptide was homologous with a class of mammalian neuropeptides that are called RF-amide neuropeptides. These endocrine signaling peptides have the consensus sequence of arginine-phenylalanine-methionine-arginine- phenylalanine (RFMRF) and end with a carboxy-terminus capped with an amide group. To investigate that observation, we have tested the ability of synthetic peptides with sequences identical to naturally occurring RF-amide neuropeptides to promote amyloid conversion of natively-folded recombinant hPrP to amyloid particles under physiological conditions. Results presented here demonstrated that synthetic RF-amide homologs were able to convert native recombinant hPrP to amyloid particles, suggesting that RF-amide neuropeptides may play a role in diseases that are associated with amyloid misfolding of the prion protein.