Cargando…

A Ca(2+)-regulated deAMPylation switch in human and bacterial FIC proteins

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 sup...

Descripción completa

Detalles Bibliográficos
Autores principales: Veyron, Simon, Oliva, Giulia, Rolando, Monica, Buchrieser, Carmen, Peyroche, Gérald, Cherfils, Jacqueline
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6408439/
https://www.ncbi.nlm.nih.gov/pubmed/30850593
http://dx.doi.org/10.1038/s41467-019-09023-1
_version_ 1783401754987069440
author Veyron, Simon
Oliva, Giulia
Rolando, Monica
Buchrieser, Carmen
Peyroche, Gérald
Cherfils, Jacqueline
author_facet Veyron, Simon
Oliva, Giulia
Rolando, Monica
Buchrieser, Carmen
Peyroche, Gérald
Cherfils, Jacqueline
author_sort Veyron, Simon
collection PubMed
description 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.
format Online
Article
Text
id pubmed-6408439
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-64084392019-03-11 A Ca(2+)-regulated deAMPylation switch in human and bacterial FIC proteins Veyron, Simon Oliva, Giulia Rolando, Monica Buchrieser, Carmen Peyroche, Gérald Cherfils, Jacqueline Nat Commun Article 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. Nature Publishing Group UK 2019-03-08 /pmc/articles/PMC6408439/ /pubmed/30850593 http://dx.doi.org/10.1038/s41467-019-09023-1 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Veyron, Simon
Oliva, Giulia
Rolando, Monica
Buchrieser, Carmen
Peyroche, Gérald
Cherfils, Jacqueline
A Ca(2+)-regulated deAMPylation switch in human and bacterial FIC proteins
title A Ca(2+)-regulated deAMPylation switch in human and bacterial FIC proteins
title_full A Ca(2+)-regulated deAMPylation switch in human and bacterial FIC proteins
title_fullStr A Ca(2+)-regulated deAMPylation switch in human and bacterial FIC proteins
title_full_unstemmed A Ca(2+)-regulated deAMPylation switch in human and bacterial FIC proteins
title_short A Ca(2+)-regulated deAMPylation switch in human and bacterial FIC proteins
title_sort ca(2+)-regulated deampylation switch in human and bacterial fic proteins
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6408439/
https://www.ncbi.nlm.nih.gov/pubmed/30850593
http://dx.doi.org/10.1038/s41467-019-09023-1
work_keys_str_mv AT veyronsimon aca2regulateddeampylationswitchinhumanandbacterialficproteins
AT olivagiulia aca2regulateddeampylationswitchinhumanandbacterialficproteins
AT rolandomonica aca2regulateddeampylationswitchinhumanandbacterialficproteins
AT buchriesercarmen aca2regulateddeampylationswitchinhumanandbacterialficproteins
AT peyrochegerald aca2regulateddeampylationswitchinhumanandbacterialficproteins
AT cherfilsjacqueline aca2regulateddeampylationswitchinhumanandbacterialficproteins
AT veyronsimon ca2regulateddeampylationswitchinhumanandbacterialficproteins
AT olivagiulia ca2regulateddeampylationswitchinhumanandbacterialficproteins
AT rolandomonica ca2regulateddeampylationswitchinhumanandbacterialficproteins
AT buchriesercarmen ca2regulateddeampylationswitchinhumanandbacterialficproteins
AT peyrochegerald ca2regulateddeampylationswitchinhumanandbacterialficproteins
AT cherfilsjacqueline ca2regulateddeampylationswitchinhumanandbacterialficproteins