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Intrinsic regulation of FIC-domain AMP-transferases by oligomerization and automodification

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 > Structural Biology & Biophysics > Structural Biology (Schirmer)
UniBasel Contributors:Schirmer, Tilman and Stanger, Frédéric and Burmann, Björn M. and Harms, Alexander and Aragao Correia, Hugo and Mazur, Adam and Sharpe, Timothy and Dehio, Christoph and Hiller Odermatt, Sebastian and Podvinec, Michael
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
Identification Number:
Last Modified:19 Dec 2017 13:22
Deposited On:29 Sep 2016 06:32

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