Ribosome-associated protein folding activity (PFAR) (PFAR)

The ribosome-associated protein folding activity (PFAR) is an intrinsic catalytic function of the large ribosomal subunit, specifically mediated by the Domain V of the 23S (prokaryotic) or 28S (eukaryotic) ribosomal RNA (Blondel et al., 2003). While the ribosome is primarily known for its role in peptide bond formation, PFAR facilitates the correct folding of nascent polypeptides as they emerge from the ribosomal exit tunnel, acting as a ribozyme-based chaperone (Reis et al., 2011). This activity is distinct from the peptidyl transferase center and is essential for maintaining cellular proteostasis. PFAR has been implicated in the pathogenesis of protein misfolding diseases, such as prion diseases and Alzheimer's, where it may inadvertently stabilize or promote the formation of toxic protein aggregates (Tribouillard-Tanvier et al., 2008). Small molecules like 6-aminophenanthridine (6AP), Guanabenz, and Imiquimod have been identified as specific inhibitors of PFAR, demonstrating therapeutic potential by reducing the formation of prions and amyloid-like aggregates without significantly affecting global translation (Voisset et al., 2011). Targeting PFAR offers a novel strategy for treating neurodegenerative proteinopathies by intervening at the very site of protein synthesis and initial folding.

Other names

Protein folding activity of the ribosomeRibosome-mediated protein foldingrRNA-mediated protein foldingRibosomal chaperone activity

Inhibition of the ribosomal RNA-mediated protein folding activity by binding to the Domain V of the large ribosomal subunit.