Characterisation of sequence-structure-function space in sensor-effector integrators of phytochrome-regulated
Cornelia Böhm1,2, Geoffrey Gourinchas1,3, Sophie Zweytick1
1Institute of Biochemistry, Graz University of Technology, 8010, Graz, Austria.
The length and composition of coiled-coil linkers in bacterial light sensors (PadCs) dictate their function and evolution. These linkers are crucial for signal integration and regulating enzyme activity, offering potential for optogenetic tools.
Area of Science:
- Biochemistry and Molecular Biology
- Protein Science
- Microbial Physiology
Background:
- Protein sequence, structure, and function are intricately linked, with dynamics playing a key role in signal transduction.
- Bacterial light sensors, specifically phytochrome-activated diguanylate cyclases (PadCs), utilize a coiled-coil linker to connect sensory and output modules for signal integration.
Purpose of the Study:
- To investigate the role of linker length and composition in determining sensor-effector function within PadC subfamily.
- To understand how linker elements influence signal integration, dynamic range, and enzyme activity regulation.
- To explore the evolutionary pressures on linker elements and their coevolution with sensory modules.
Main Methods:
- Phylogenetic analyses of PadC homologs.
- Biochemical characterization of PadC subfamily members.
- Analysis of linker length, composition, and their impact on protein function.
Main Results:
- Linker length and composition significantly determine PadC sensor-effector function and are under evolutionary pressure.
- Linker characteristics, along with the PHY domain, modulate effector activation dynamics and can lead to enzyme inhibition.
- Phylogenetic clustering based on linker length and the emergence of new functions within linker families were observed.
Conclusions:
- The coiled-coil linker acts as a critical signal integrator, directly regulating diguanylate cyclase activity.
- Functional coupling between the PHY dimer interface and linker element is essential for signal integration and output regulation.
- Understanding these linkers provides a foundation for designing novel optogenetic tools using diverse PadC homologs.
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