Activation of a secondary-messenger receptor via allosteric modulation of a dynamic conformational ensemble

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dc.contributor.authorSöldner, Benedikt
dc.contributor.authorSingh, Himanshu
dc.contributor.authorAkoury, Elias
dc.contributor.authorWitte, Gregor
dc.contributor.authorLinser, Rasmus
dc.date.accessioned2026-01-15T07:18:21Z
dc.date.available2026-01-15T07:18:21Z
dc.date.issued2025-08-06
dc.description.abstractBacterial signaling cascades have recently become of great relevance in the context of bacterial antibiotics resistance. Cyclic diadenylate monophosphate (c-di-AMP) is a key bacterial secondary messenger involved in growth, biofilm formation, virulence gene expression and others. The activation mechanisms of c-di-AMP receptors like the trimeric PII-like proteins upon messenger binding have, however, remained elusive due the pivotal role of highly flexible protein regions. Here, using solution NMR spectroscopy to elucidate the interplay between the ordered and disordered structural elements of the apo and messenger-bound forms of the 44 kDa homotrimeric PII-like signal transduction protein A (PstA), we reveal a sensitive modulation of the conformational ensemble of those extended loops thought to bind the downstream interaction partners by messenger association at the receptor core. The orchestration of the spatial properties of the loops, despite their retained internal dynamics, reveals the importance of allosteric effects even for disordered structural elements, whose steerable ensemble properties have long escaped the classical structural-biology understanding.en
dc.identifier.urihttp://hdl.handle.net/2003/44675
dc.language.isoen
dc.relation.ispartofseriesAngewandte Chemie / International edition; 64(38)
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectConformational exchangeen
dc.subjectCyclic-di-AMPen
dc.subjectNuclear magnetic resonance spectroscopyen
dc.subjectProtein dynamicsen
dc.subjectSecondary messengersen
dc.subject.ddc540
dc.subject.rswkKonformationsänderung
dc.subject.rswkCyclisches di-AMP
dc.subject.rswkNMR-Spektroskopie
dc.subject.rswkProteine
dc.subject.rswkBotenmolekül
dc.titleActivation of a secondary-messenger receptor via allosteric modulation of a dynamic conformational ensembleen
dc.typeText
dc.type.publicationtypeResearchArticle
dcterms.accessRightsopen access
eldorado.dnb.deposittrue
eldorado.doi.registerfalse
eldorado.openaire.projectidentifierinfo:eu-repo/grantAgreement/EC/HE/101082494/EU/Fast-MAS Solid-State NMR as a Bypass to High-Molecular-Weight Proteins in Solution/bypassNMR/
eldorado.secondarypublicationtrue
eldorado.secondarypublication.primarycitationB. Söldner, H. Singh, E. Akoury, G. Witte, R. Linser, Angew. Chem. Int. Ed.. 2025, 64, e202509394. https://doi.org/10.1002/anie.202509394
eldorado.secondarypublication.primaryidentifierhttps://doi.org/10.1002/anie.202509394

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