5nwf

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Enterococcus faecalis FIC protein (H111A).Enterococcus faecalis FIC protein (H111A).

Structural highlights

5nwf is a 2 chain structure with sequence from Enterococcus faecalis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.6Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

U6S0Y1_ENTFL

Publication Abstract from PubMed

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(2+) and Ca(2+) control AMPylation and deAMPylation differentially without a conformational change. Remarkably, Ca(2+) 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.

A Ca(2+)-regulated deAMPylation switch in human and bacterial FIC proteins.,Veyron S, Oliva G, Rolando M, Buchrieser C, Peyroche G, Cherfils J Nat Commun. 2019 Mar 8;10(1):1142. doi: 10.1038/s41467-019-09023-1. PMID:30850593[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. Veyron S, Oliva G, Rolando M, Buchrieser C, Peyroche G, Cherfils J. A Ca(2+)-regulated deAMPylation switch in human and bacterial FIC proteins. Nat Commun. 2019 Mar 8;10(1):1142. doi: 10.1038/s41467-019-09023-1. PMID:30850593 doi:http://dx.doi.org/10.1038/s41467-019-09023-1

5nwf, resolution 2.60Å

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OCA