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)Download file
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.
journal contributionposted 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.
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.).
CitationTHE 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
VersionVoR (Version of Record)
Published inJournal of Biological Chemistry
PublisherAmerican Society for Biochemistry and Molecular Biology
Bacterial Signal TransductionBioinformaticsComplexCrystal StructureNucleotideStaphylococcus aureus (S. aureus)ATP-Binding Cassette TransportersAmino Acid SequenceBacterial ProteinsCarrier ProteinsComputational BiologyMolecular Sequence DataProtein Structure, SecondaryProtein Structure, TertiarySequence Homology, Amino AcidSignal TransductionStaphylococcus aureus