ERAD substrate recognition in budding yeast.
During protein synthesis, the orderly progression of folding, modification, and assembly is paramount to function and vis-à-vis cellular viability. Accordingly, sophisticated quality control mechanisms have evolved to monitor protein maturation throughout the cell. Proteins failing at any step are segregated and degraded as a preventative measure against potential toxicity. Although protein quality control is generally poorly understood, recent research advances in endoplasmic reticulum-associated degradation (ERAD) pathways have provided the most detailed view so far. The discovery of distinct substrate processing sites established a biochemical basis for genetic profiles of model misfolded proteins. Detailed mechanisms for substrate recognition were recently uncovered. For some proteins, sequential glycan trimming steps set a time window for folding. Proteins still unfolded at the final stage expose a specific degradation signal recognized by the ERAD machinery. Through this mechanism, the system does not in fact know that a molecule is "misfolded". Instead, it goes by the premise that proteins past due have veered off their normal folding pathways and therefore aberrant.
Xie
Wei
W
Temasek Life Sciences Laboratory and Department of Biological Sciences, National University of Singapore, 1 Research Link, Singapore 117604, Singapore.
Ng
Davis T W
DT
D000818:Animals; D002352:Carrier Proteins; D004721:Endoplasmic Reticulum / Q000235:genetics / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D004718:Saccharomycetales / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics
D002352:Carrier Proteins; D011506:Proteins; C479529:RBX1 protein, human