Proline/arginine dipeptide repeat polymers derail protein folding in amyotrophic lateral sclerosis

The most frequent cause of familial Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD) are hexanucleotide repeat expansions in 7 Piece King Panel Bedroom Package the non-coding region of the C9ORF72 gene that are translated into five dipeptide repeat (DPR) proteins.Here, the authors show that proline/arginine (PR) DPRs inhibit the prolyl isomerase PPIA Printed Leather Wallet and reveal the molecular mechanism of the impaired protein folding activity of PPIA by performing NMR measurements and determining a PR DPR bound PPIA crystal structure.