Engineering of a red-light–activated human cAMP/cGMP-specific phosphodiesterase
| العنوان: | Engineering of a red-light–activated human cAMP/cGMP-specific phosphodiesterase |
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| المؤلفون: | Chen-Min Yeh, Charlotte Helene Wittig, Carlos Gasser, Sandra Taiber, Frank Wunder, Peter Hegemann, Soojin Ryu, Andreas Möglich |
| المصدر: | Proceedings of the National Academy of Sciences. 111:8803-8808 |
| بيانات النشر: | Proceedings of the National Academy of Sciences, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Models, Molecular, Light, Recombinant Fusion Proteins, Adenylate kinase, CHO Cells, Optogenetics, Biology, Protein Engineering, Cell Line, chemistry.chemical_compound, Cricetulus, Genes, Reporter, Cricetinae, Cyclic AMP, Escherichia coli, Animals, Humans, Cyclic GMP, Zebrafish, Multidisciplinary, Biliverdin, Phytochrome, Light sensitivity, Phosphoric Diester Hydrolases, Effector, Hydrolysis, Synechocystis, Temperature, Phosphodiesterase, Biological Sciences, Cyclic Nucleotide Phosphodiesterases, Type 2, Protein Structure, Tertiary, Cell biology, Kinetics, chemistry, Biochemistry, Second messenger system, Allosteric Site |
| الوصف: | Sensory photoreceptors elicit vital physiological adaptations in response to incident light. As light-regulated actuators, photoreceptors underpin optogenetics, which denotes the noninvasive, reversible, and spatiotemporally precise perturbation by light of living cells and organisms. Of particular versatility, naturally occurring photoactivated adenylate cyclases promote the synthesis of the second messenger cAMP under blue light. Here, we have engineered a light-activated phosphodiesterase (LAPD) with complementary light sensitivity and catalytic activity by recombining the photosensor module of Deinococcus radiodurans bacterial phytochrome with the effector module of Homo sapiens phosphodiesterase 2A. Upon red-light absorption, LAPD up-regulates hydrolysis of cAMP and cGMP by up to sixfold, whereas far-red light can be used to down-regulate activity. LAPD also mediates light-activated cAMP and cGMP hydrolysis in eukaryotic cell cultures and in zebrafish embryos; crucially, the biliverdin chromophore of LAPD is available endogenously and does not need to be provided exogenously. LAPD thus establishes a new optogenetic modality that permits light control over diverse cAMP/cGMP-mediated physiological processes. Because red light penetrates tissue more deeply than light of shorter wavelengths, LAPD appears particularly attractive for studies in living organisms. |
| تدمد: | 1091-6490 0027-8424 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::57420903c20d74ad79e13cffb749c4acTest https://doi.org/10.1073/pnas.1321600111Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....57420903c20d74ad79e13cffb749c4ac |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10916490 00278424 |
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