Unfolded or misfolded client protein

Unfolded or misfolded client proteins are polypeptides that have failed to achieve or maintain their proper three-dimensional (native) conformation, either due to mutations, cellular stress, or errors in folding pathways[7][4][1]. These proteins are recognized by molecular chaperones (such as Hsp70, Hsp90, and GroEL), which attempt to refold them or direct them for degradation, thus maintaining cellular proteostasis[3][1][5]. Accumulation of such proteins triggers the cellular unfolded protein response (UPR) and can lead to toxic aggregation implicated in neurodegenerative and protein misfolding diseases[7][1][5]. While molecules that modulate chaperone activity or proteostasis pathways are being developed as therapeutics, unfolded/misfolded client proteins themselves are not direct, tractable drug targets but rather the consequence or substrate within these pathways[1][4][5]. This entry describes a *category* of substrates within the protein quality control system, and not a specific, standardized molecular entity.

Other names

Misfolded proteinUnfolded proteinAberrant proteinNon-native polypeptideClient protein (in context of chaperones)

Stabilization of folding intermediates Prevention of aggregation Enhancement of degradation of misfolded proteins Modulation of chaperone activity