Stanger, Frédéric V. and Burmann, Björn M. and Harms, Alexander and Aragão, Hugo and Mazur, Adam and Sharpe, Timothy and Dehio, Christoph and Hiller, Sebastian and Schirmer, Tilman. (2016) Intrinsic regulation of FIC-domain AMP-transferases by oligomerization and automodification. Proceedings of the National Academy of Sciences of the United States of America, 113 (5). E529-E537.
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Abstract
Filamentation induced by cyclic AMP (FIC)-domain enzymes catalyze adenylylation or other posttranslational modifications of target proteins to control their function. Recently, we have shown that Fic enzymes are autoinhibited by an α-helix (αinh) that partly obstructs the active site. For the single-domain class III Fic proteins, the αinh is located at the C terminus and its deletion relieves autoinhibition. However, it has remained unclear how activation occurs naturally. Here, we show by structural, biophysical, and enzymatic analyses combined with in vivo data that the class III Fic protein NmFic from Neisseria meningitidis gets autoadenylylated in cis, thereby autonomously relieving autoinhibition and thus allowing subsequent adenylylation of its target, the DNA gyrase subunit GyrB. Furthermore, we show that NmFic activation is antagonized by tetramerization. The combination of autoadenylylation and tetramerization results in nonmonotonic concentration dependence of NmFic activity and a pronounced lag phase in the progress of target adenylylation. Bioinformatic analyses indicate that this elaborate dual-control mechanism is conserved throughout class III Fic proteins.
Faculties and Departments: | 05 Faculty of Science > Departement Biozentrum > Former Organization Units Biozentrum > Structural Biology (Schirmer) 05 Faculty of Science > Departement Biozentrum > Structural Biology & Biophysics > Structural Biology (Hiller) 05 Faculty of Science > Departement Biozentrum > Former Organization Units Biozentrum > Molecular Microbiology (Harms) 05 Faculty of Science > Departement Biozentrum > Services Biozentrum > Research IT (Podvinec) |
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UniBasel Contributors: | Schirmer, Tilman and Stanger, Frédéric and Burmann, Björn M. and Aragao Correia, Hugo and Mazur, Adam and Sharpe, Timothy and Dehio, Christoph and Hiller, Sebastian and Podvinec, Michael and Harms, Alexander |
Item Type: | Article, refereed |
Article Subtype: | Research Article |
Publisher: | National Academy of Sciences |
ISSN: | 0027-8424 |
e-ISSN: | 1091-6490 |
Note: | Publication type according to Uni Basel Research Database: Journal article |
Language: | English |
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Last Modified: | 10 Sep 2021 03:10 |
Deposited On: | 29 Sep 2016 06:32 |
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