FICD acts bifunctionally to AMPylate and de-AMPylate the endoplasmic reticulum chaperone BiP
作者： Steffen Preissler , Claudia Rato , Luke A Perera , Vladimir Saudek , David Ron
DOI: 10.1038/NSMB.3337
关键词:
摘要: The enzyme FICD was previously known to AMPylate the ER-resident chaperone BiP, inactivating chaperone. Mammalian is now shown catalyze removal of AMP group from BiP. Protein folding homeostasis in endoplasmic reticulum (ER) defended by an unfolded protein response that matches ER capacity burden proteins. As levels proteins decline, a metazoan-specific FIC-domain-containing ER-localized (FICD) rapidly inactivates major BiP AMPylating T518. Here we show single catalytic domain can also release attached AMP, restoring functionality Consistent with role for endogenous de-AMPylating FICD−/− hamster cells are hypersensitive introduction constitutively AMPylating, de-AMPylation-defective mutant FICD. These opposing activities hinge on regulatory residue, E234, whose default state renders constitutive de-AMPylase vitro. location E234 conserved helix and mutually antagonistic vivo, suggest mechanism whereby fluctuating load actively switches AMPylase.
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