Schröder-Tittmann, Kathrin

[["dc.bibliographiccitation.firstpage","3069"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Journal of biological chemistry"],["dc.bibliographiccitation.lastpage","3080"],["dc.bibliographiccitation.volume","290"],["dc.contributor.author","Gundlach, Jan"],["dc.contributor.author","Dickmanns, Achim"],["dc.contributor.author","Schröder-Tittmann, Kathrin"],["dc.contributor.author","Neumann, Piotr"],["dc.contributor.author","Kaesler, Jan"],["dc.contributor.author","Kampf, Jan"],["dc.contributor.author","Herzberg, Christina"],["dc.contributor.author","Hammer, Elke"],["dc.contributor.author","Schwede, Frank"],["dc.contributor.author","Kaever, Volkhard"],["dc.contributor.author","Tittmann, Kai"],["dc.contributor.author","Stülke, Jörg"],["dc.contributor.author","Ficner, Ralf"],["dc.date.accessioned","2017-09-07T11:44:39Z"],["dc.date.available","2017-09-07T11:44:39Z"],["dc.date.issued","2015"],["dc.description.abstract","Background: Cyclic di-AMP is an essential second messenger in eubacteria. Results: The c-di-AMP receptor DarA was identified in B. subtilis. The crystal structure and ITC data revealed the nucleotide specificity of DarA. Conclusion: DarA is a P-II-like protein that undergoes conformational changes upon c-di-AMP binding. Significance: A novel P-II-like protein is involved in c-di-AMP signaling. The cyclic dimeric AMP nucleotide c-di-AMP is an essential second messenger in Bacillus subtilis. We have identified the protein DarA as one of the prominent c-di-AMP receptors in B. subtilis. Crystal structure analysis shows that DarA is highly homologous to P-II signal transducer proteins. In contrast to P-II proteins, the functionally important B- and T-loops are swapped with respect to their size. DarA is a homotrimer that binds three molecules of c-di-AMP, each in a pocket located between two subunits. We demonstrate that DarA is capable to bind c-di-AMP and with lower affinity cyclic GMP-AMP (33-cGAMP) but not c-di-GMP or 23-cGAMP. Consistently the crystal structure shows that within the ligand-binding pocket only one adenine is highly specifically recognized, whereas the pocket for the other adenine appears to be promiscuous. Comparison with a homologous ligand-free DarA structure reveals that c-di-AMP binding is accompanied by conformational changes of both the fold and the position of the B-loop in DarA."],["dc.identifier.doi","10.1074/jbc.M114.619619"],["dc.identifier.gro","3141969"],["dc.identifier.isi","000349310700043"],["dc.identifier.pmid","25433025"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/3090"],["dc.notes.intern","WoS Import 2017-03-10 / Funder: Deutsche Forschungsgemeinschaft [HI 291/13-1, SFB860]"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.eissn","1083-351X"],["dc.relation.issn","0021-9258"],["dc.title","Identification, Characterization, and Structure Analysis of the Cyclic di-AMP-binding P-II-like Signal Transduction Protein DarA"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","21098"],["dc.bibliographiccitation.issue","30"],["dc.bibliographiccitation.journal","Journal of Biological Chemistry"],["dc.bibliographiccitation.lastpage","21107"],["dc.bibliographiccitation.volume","289"],["dc.contributor.author","Mehne, Felix M. P."],["dc.contributor.author","Schroeder-Tittmann, Kathrin"],["dc.contributor.author","Eijlander, Robyn T."],["dc.contributor.author","Herzberg, Christina"],["dc.contributor.author","Hewitt, Lorraine"],["dc.contributor.author","Kaever, Volkhard"],["dc.contributor.author","Lewis, Richard J."],["dc.contributor.author","Kuipers, Oscar P."],["dc.contributor.author","Tittmann, Kai"],["dc.contributor.author","Stuelke, Joerg"],["dc.date.accessioned","2018-11-07T09:37:31Z"],["dc.date.available","2018-11-07T09:37:31Z"],["dc.date.issued","2014"],["dc.description.abstract","The Gram-positive bacterium Bacillus subtilis encodes three diadenylate cyclases that synthesize the essential signaling nucleotide cyclic di-AMP. The activities of the vegetative enzymes DisA and CdaA are controlled by protein-protein interactions with their conserved partner proteins. Here, we have analyzed the regulation of the unique sporulation-specific diadenylate cyclase CdaS. Very low expression of CdaS as the single diadenylate cyclase resulted in the appearance of spontaneous suppressor mutations. Several of these mutations in the cdaS gene affected the N-terminal domain of CdaS. The corresponding CdaS mutant proteins exhibited a significantly increased enzymatic activity. The N-terminal domain of CdaS consists of two alpha-helices and is attached to the C-terminal catalytically active diadenylate cyclase (DAC) domain. Deletion of the first or both helices resulted also in strongly increased activity indicating that the N-terminal domain serves to limit the enzyme activity of the DAC domain. The structure of YojJ, a protein highly similar to CdaS, indicates that the protein forms hexamers that are incompatible with enzymatic activity of the DAC domains. In contrast, the mutations and the deletions of the N-terminal domain result in conformational changes that lead to highly increased enzymatic activity. Although the full-length CdaS protein was found to form hexamers, a truncated version with a deletion of the first N-terminal helix formed dimers with high enzyme activity. To assess the role of CdaS in sporulation, we assayed the germination of wild type and cdaS mutant spores. The results indicate that cyclic di-AMP formed by CdaS is required for efficient germination."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft [SFB860]"],["dc.identifier.doi","10.1074/jbc.M114.562066"],["dc.identifier.isi","000339396600060"],["dc.identifier.pmid","24939848"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/32860"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Soc Biochemistry Molecular Biology Inc"],["dc.relation.issn","1083-351X"],["dc.relation.issn","0021-9258"],["dc.title","Control of the Diadenylate Cyclase CdaS in Bacillus subtilis AN AUTOINHIBITORY DOMAIN LIMITS CYCLIC DI-AMP PRODUCTION"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]