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

Author

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  • 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
    Sorbonne Université, Collège doctoral)

  • 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)

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.

Suggested Citation

  • Simon Veyron & Giulia Oliva & Monica Rolando & Carmen Buchrieser & Gérald Peyroche & Jacqueline Cherfils, 2019. "A Ca2+-regulated deAMPylation switch in human and bacterial FIC proteins," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09023-1
    DOI: 10.1038/s41467-019-09023-1
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    Cited by:

    1. Dandan Wang & Lingfang Zhu & Xiangkai Zhen & Daoyan Yang & Changfu Li & Yating Chen & Huannan Wang & Yichen Qu & Xiaozhen Liu & Yanling Yin & Huawei Gu & Lei Xu & Chuanxing Wan & Yao Wang & Songying O, 2022. "A secreted effector with a dual role as a toxin and as a transcriptional factor," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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