Complex structure and biochemical characterization of the Staphylococcus aureus cyclic diadenylate monophosphate (c-di-AMP)-binding protein PstA, the founding member of a new signal transduction protein family.pdf (2.99 MB)
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Complex structure and biochemical characterization of the Staphylococcus aureus cyclic diadenylate monophosphate (c-di-AMP)-binding protein PstA, the founding member of a new signal transduction protein family.

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journal contribution
posted on 22.07.2020, 09:32 by I Campeotto, Y Zhang, MG Mladenov, PS Freemont, A Gründling
Signaling nucleotides are integral parts of signal transduction systems allowing bacteria to cope with and rapidly respond to changes in the environment. The Staphylococcus aureus PII-like signal transduction protein PstA was recently identified as a cyclic diadenylate monophosphate (c-di-AMP)-binding protein. Here, we present the crystal structures of the apo- and c-di-AMP-bound PstA protein, which is trimeric in solution as well as in the crystals. The structures combined with detailed bioinformatics analysis revealed that the protein belongs to a new family of proteins with a similar core fold but with distinct features to classical PII proteins, which usually function in nitrogen metabolism pathways in bacteria. The complex structure revealed three identical c-di-AMP-binding sites per trimer with each binding site at a monomer-monomer interface. Although distinctly different from other cyclic-di-nucleotide-binding sites, as the half-binding sites are not symmetrical, the complex structure also highlighted common features for c-di-AMP-binding sites. A comparison between the apo and complex structures revealed a series of conformational changes that result in the ordering of two anti-parallel β-strands that protrude from each monomer and allowed us to propose a mechanism on how the PstA protein functions as a signaling transduction protein.

Funding

This work was supported by European Research Council Grant 260371, Wellcome Trust Grant 100289 (to A. G.), and the EMBO Long Term Fellowship ALTF 721-2013 (to Y. Z.).

History

Citation

THE JOURNAL OF BIOLOGICAL CHEMISTRY VOL. 290, NO. 5, pp. 2888 –2901, January 30, 2015

Author affiliation

/Organisation/COLLEGE OF LIFE SCIENCES/Biological Sciences/Molecular & Cell Biology

Version

VoR (Version of Record)

Published in

Journal of Biological Chemistry

Volume

290

Issue

5

Pagination

2888 –2901

Publisher

American Society for Biochemistry and Molecular Biology

issn

0021-9258

eissn

1083-351X

Acceptance date

29/10/2014

Copyright date

2014

Available date

22/07/2020

Language

eng

Publisher version

https://www.jbc.org/content/290/5/2888.short