Title data
Möglich, Andreas ; Ayers, Rebecca A. ; Moffat, Keith:
Addition at the molecular level : signal integration in designed Per-ARNT-Sim receptor proteins.
In: Journal of Molecular Biology.
Vol. 400
(2010)
Issue 3
.
- pp. 477-486.
ISSN 0022-2836
DOI: https://doi.org/10.1016/j.jmb.2010.05.019
Project information
Project financing: |
National Institutes of Health |
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Abstract in another language
Survival of organisms in dynamic environments requires accurate perception and integration of signals. At the molecular level, signal detection is mediated by signal receptor proteins that largely are of modular composition. Sensor modules, such as the widespread Per-ARNT-Sim (PAS) domains, detect signals and, in response, regulate the biological activity of effector modules. Here, we exploit the modularity of signal receptors to design and engineer synthetic receptors that comprise two PAS sensor domains responsive to different signals, and we use these signals to control the activity of a histidine kinase effector. Designed two-input PAS receptors detected oxygen and blue light in a positive cooperative manner. The extent of the response to the signals was dictated by domain topology: the dominant regulatory effect was exerted by the PAS domain proximal to the effector domain. The presence of one sensor domain modulated the signal response function of the other. Sequence and structural data on natural receptors with tandem PAS domains show that these are predominantly linked by short amphipathic alpha-helices. Signals from multiple sensor domains could be integrated and propagated to the effector domain as torques. Our results inform the rational design of receptors that integrate multiple signals to modulate cellular behavior.
Further data
Item Type: | Article in a journal |
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Refereed: | Yes |
Additional notes: | PubMed-ID: 20471402 |
Institutions of the University: | Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Chair Biochemistry > Chair Biochemistry - Univ.-Prof. Dr. Andreas Möglich Faculties Faculties > Faculty of Biology, Chemistry and Earth Sciences Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Professorship Biochemistry Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Chair Biochemistry |
Result of work at the UBT: | No |
DDC Subjects: | 500 Science > 540 Chemistry |
Date Deposited: | 19 May 2015 08:32 |
Last Modified: | 11 Jul 2022 13:20 |
URI: | https://eref.uni-bayreuth.de/id/eprint/13602 |