6EP0

Enterococcus faecalis FIC protein in complex with AMP and calcium ion.

6EP0 の概要

• エントリーDOI: 10.2210/pdb6ep0/pdb
• 関連するPDBエントリー: 5NUW
• 分子名称: Fic family protein, ADENOSINE MONOPHOSPHATE, CALCIUM ION, ... (5 entities in total)
• 機能のキーワード: toxin
• 由来する生物種: Enterococcus faecalis
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 50278.05

構造登録者

Veyron, S.,Cherfils, J. (登録日: 2017-10-10, 公開日: 2019-02-06, 最終更新日: 2024-01-17)

主引用文献

Veyron, S.,Oliva, G.,Rolando, M.,Buchrieser, C.,Peyroche, G.,Cherfils, J.
A Ca2+-regulated deAMPylation switch in human and bacterial FIC proteins.
Nat Commun, 10:1142-1142, 2019

PubMed Abstract: FIC proteins regulate molecular processes from bacteria to humans by catalyzing post-translational modifications (PTM), the most frequent being the addition of AMP or AMPylation. In many AMPylating FIC proteins, a structurally conserved glutamate represses AMPylation and, in mammalian FICD, also supports deAMPylation of BiP/GRP78, a key chaperone of the unfolded protein response. Currently, a direct signal regulating these FIC proteins has not been identified. Here, we use X-ray crystallography and in vitro PTM assays to address this question. We discover that Enterococcus faecalis FIC (EfFIC) catalyzes both AMPylation and deAMPylation and that the glutamate implements a multi-position metal switch whereby Mg and Ca control AMPylation and deAMPylation differentially without a conformational change. Remarkably, Ca concentration also tunes deAMPylation of BiP by human FICD. Our results suggest that the conserved glutamate is a signature of AMPylation/deAMPylation FIC bifunctionality and identify metal ions as diffusible signals that regulate such FIC proteins directly.

PubMed: 30850593
DOI: 10.1038/s41467-019-09023-1

実験手法

X-RAY DIFFRACTION (2.35 Å)