6I7L

Crystal structure of monomeric FICD mutant L258D complexed with MgAMP-PNP

6I7L の概要

• エントリーDOI: 10.2210/pdb6i7l/pdb
• 分子名称: Adenosine monophosphate-protein transferase FICD, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, MAGNESIUM ION, ... (4 entities in total)
• 機能のキーワード: fic, ampylation, upr, bip, transferase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 39981.55

構造登録者

Perera, L.A.,Yan, Y.,Read, R.J.,Ron, D. (登録日: 2018-11-16, 公開日: 2019-09-25, 最終更新日: 2024-01-24)

主引用文献

Perera, L.A.,Rato, C.,Yan, Y.,Neidhardt, L.,McLaughlin, S.H.,Read, R.J.,Preissler, S.,Ron, D.
An oligomeric state-dependent switch in the ER enzyme FICD regulates AMPylation and deAMPylation of BiP.
Embo J., 38:e102177-e102177, 2019

PubMed Abstract: AMPylation is an inactivating modification that alters the activity of the major endoplasmic reticulum (ER) chaperone BiP to match the burden of unfolded proteins. A single ER-localised Fic protein, FICD (HYPE), catalyses both AMPylation and deAMPylation of BiP. However, the basis for the switch in FICD's activity is unknown. We report on the transition of FICD from a dimeric enzyme, that deAMPylates BiP, to a monomer with potent AMPylation activity. Mutations in the dimer interface, or of residues along an inhibitory pathway linking the dimer interface to the enzyme's active site, favour BiP AMPylation in vitro and in cells. Mechanistically, monomerisation relieves a repressive effect allosterically propagated from the dimer interface to the inhibitory Glu234, thereby permitting AMPylation-competent binding of MgATP. Moreover, a reciprocal signal, propagated from the nucleotide-binding site, provides a mechanism for coupling the oligomeric state and enzymatic activity of FICD to the energy status of the ER.

PubMed: 31531998
DOI: 10.15252/embj.2019102177

実験手法

X-RAY DIFFRACTION (2.32 Å)