Futile Protein Folding Cycles in the ER Are Terminated by the Unfolded Protein O-Mannosylation Pathway

Abstract

Folding Too Slow, Off You Go One of the major questions of chaperone-assisted protein-folding pathways is how substrates that fail to fold avoid futile folding cycles. Xu et al. (p. 978 ; see the Perspective by Kleizen and Braakman ) developed a model to examine a folding-competent protein that nevertheless fails to fold within the endoplasmic reticulum. Under these circumstances, the unfolded protein was subject to an unusual glycosylation, O-mannosylation, which appeared to terminate folding of the unfinished molecules. Eliminating O-mannosylation allowed the protein to fold completely.