7B80

DeAMPylation complex of monomeric FICD and AMPylated BiP (state 2)

7B80 の概要

• エントリーDOI: 10.2210/pdb7b80/pdb
• 分子名称: Endoplasmic reticulum chaperone BiP, Protein adenylyltransferase FICD, ADENOSINE MONOPHOSPHATE, ... (9 entities in total)
• 機能のキーワード: ficd, fic, hype, bip, grp78, ampylation, deampylation, deampylase, er stress, complex, adenylation, adenylylation, hsp70, chaperone, transferase, hydrolase
• 由来する生物種: Cricetulus griseus (Chinese hamster); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 98400.13

構造登録者

Perera, L.A.,Ron, D. (登録日: 2020-12-12, 公開日: 2021-07-07, 最終更新日: 2024-10-23)

主引用文献

Perera, L.A.,Preissler, S.,Zaccai, N.R.,Prevost, S.,Devos, J.M.,Haertlein, M.,Ron, D.
Structures of a deAMPylation complex rationalise the switch between antagonistic catalytic activities of FICD.
Nat Commun, 12:5004-5004, 2021

PubMed Abstract: The endoplasmic reticulum (ER) Hsp70 chaperone BiP is regulated by AMPylation, a reversible inactivating post-translational modification. Both BiP AMPylation and deAMPylation are catalysed by a single ER-localised enzyme, FICD. Here we present crystallographic and solution structures of a deAMPylation Michaelis complex formed between mammalian AMPylated BiP and FICD. The latter, via its tetratricopeptide repeat domain, binds a surface that is specific to ATP-state Hsp70 chaperones, explaining the exquisite selectivity of FICD for BiP's ATP-bound conformation both when AMPylating and deAMPylating Thr518. The eukaryotic deAMPylation mechanism thus revealed, rationalises the role of the conserved Fic domain Glu234 as a gatekeeper residue that both inhibits AMPylation and facilitates hydrolytic deAMPylation catalysed by dimeric FICD. These findings point to a monomerisation-induced increase in Glu234 flexibility as the basis of an oligomeric state-dependent switch between FICD's antagonistic activities, despite a similar mode of engagement of its two substrates - unmodified and AMPylated BiP.

PubMed: 34408154
DOI: 10.1038/s41467-021-25076-7

実験手法

X-RAY DIFFRACTION (1.87 Å)