6ER8

Enterococcus faecalis FIC protein in complex with phosphate.

Summary for 6ER8

• Entry DOI: 10.2210/pdb6er8/pdb
• Descriptor: Fic family protein, ACETATE ION, PHOSPHATE ION, ... (4 entities in total)
• Functional Keywords: fic, ampylation, toxin
• Biological source: Enterococcus faecalis
• Total number of polymer chains: 2
• Total formula weight: 49521.22

Authors

Veyron, S.,Cherfils, J. (deposition date: 2017-10-17, release date: 2019-02-06, Last modification date: 2024-01-17)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.292 Å)