A Ca2+-regulated deAMPylation switch in human and bacterial FIC proteins

Simon Veyron, Giulia Oliva, Monica Rolando, Carmen Buchrieser, Gérald Peyroche and Jacqueline Cherfils ()
Additional contact information
Simon Veyron: CNRS and Ecole normale supérieure Paris-Saclay, Laboratoire de Biologie et Pharmacologie Appliquée
Giulia Oliva: Institut Pasteur and CNRS UMR 3525, Biologie des Bactéries Intracellulaires
Monica Rolando: Institut Pasteur and CNRS UMR 3525, Biologie des Bactéries Intracellulaires
Carmen Buchrieser: Institut Pasteur and CNRS UMR 3525, Biologie des Bactéries Intracellulaires
Gérald Peyroche: CNRS and Ecole normale supérieure Paris-Saclay, Laboratoire de Biologie et Pharmacologie Appliquée
Jacqueline Cherfils: CNRS and Ecole normale supérieure Paris-Saclay, Laboratoire de Biologie et Pharmacologie Appliquée

Nature Communications, 2019, vol. 10, issue 1, 1-10

Abstract: 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 Mg2+ and Ca2+ control AMPylation and deAMPylation differentially without a conformational change. Remarkably, Ca2+ 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.

Date: 2019
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-019-09023-1 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09023-1

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-019-09023-1

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().