The luminal domain of the ER stress sensor protein PERK binds misfolded proteins and thereby triggers PERK oligomerization.

ABSTRACT: PRKR-like endoplasmic reticulum kinase (PERK) is one of the major sensor proteins that detect protein folding imbalances during endoplasmic reticulum (ER) stress. However, it remains unclear how ER stress activates PERK to initiate a downstream unfolded protein response (UPR). Here, we found that PERK's luminal domain can recognize and selectively interact with misfolded proteins but not with native proteins. Screening a phage-display library, we identified a peptide substrate, P16, of the PERK luminal domain and confirmed that P16 efficiently competes with misfolded proteins for binding this domain. To unravel the mechanism by which the PERK luminal domain interacts with misfolded proteins, we determined the crystal structure of the bovine PERK luminal domain complexed with P16 to 2.8-Å r

SUBMITTER: Wang P 

PROVIDER: S-EPMC5857997 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature