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Abstract
Understanding the relationship between protein sequence, structure and function is one of the fundamental challenges in biochemistry. A direct correlation, however, is often not trivial since protein dynamics also play an important functional role—especially in signal transduction processes. In a subfamily of bacterial light sensors, phytochrome-activated diguanylate cyclases (PadCs), a characteristic coiled-coil linker element connects photoreceptor and output module, playing an essential role in signal integration. Combining phylogenetic analyses with biochemical characterisations, we were able to show that length and composition of this linker determine sensor–effector function and as such are under considerable evolutionary pressure. The linker length, together with the upstream PHY-specific domain, influences the dynamic range of effector activation and can even cause light-induced enzyme inhibition. We demonstrate phylogenetic clustering according to linker length, and the development of new linker lengths as well as new protein function within linker families. The biochemical characterisation of PadC homologs revealed that the functional coupling of PHY dimer interface and linker element defines signal integration and regulation of output functionality. A small subfamily of PadCs, characterised by a linker length breaking the coiled-coil pattern, shows a markedly different behaviour from other homologs. The effect of the central helical spine on PadC function highlights its essential role in signal integration as well as direct regulation of diguanylate cyclase activity. Appreciation of sensor–effector linkers as integrator elements and their coevolution with sensory modules is a further step towards the use of functionally diverse homologs as building blocks for rationally designed optogenetic tools.
Originalsprache | englisch |
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Seiten (von - bis) | 1761-1779 |
Seitenumfang | 19 |
Fachzeitschrift | Photochemical & Photobiological Sciences |
Jahrgang | 21 |
Ausgabenummer | 10 |
DOIs | |
Publikationsstatus | Veröffentlicht - Okt. 2022 |
ASJC Scopus subject areas
- Physikalische und Theoretische Chemie
Fields of Expertise
- Human- & Biotechnology
Kooperationen
- BioTechMed-Graz
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Untersuchen Sie die Forschungsthemen von „Characterisation of sequence–structure–function space in sensor–effector integrators of phytochrome-regulated diguanylate cyclases“. Zusammen bilden sie einen einzigartigen Fingerprint.Projekte
- 1 Abgeschlossen
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FWF - PadC - Signaltransduktion in Phytochrom-Diguanylatzyklase Systemen
1/02/19 → 31/01/24
Projekt: Forschungsprojekt
Aktivitäten
- 1 Vortrag bei Konferenz oder Fachtagung
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Characterization of Sequence-Structure-Function Relationships in Phytochrome Regulated Diguanylate Cyclases
Cornelia Böhm (Redner/in), Geoffrey Gourinchas (Beitragende/r), Christoph Wilhelm Sensen (Beitragende/r) & Andreas Winkler (Beitragende/r)
7 Juli 2022Aktivität: Vortrag oder Präsentation › Vortrag bei Konferenz oder Fachtagung › Science to science