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...
Autores principales: | , , , , , |
---|---|
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 |