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

Proceedings of the National Academy of Sciences of the United States of America
Frédéric Valentin StangerTilman Schirmer

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.

References

Nov 1, 1995·Journal of Biomolecular NMR·F DelaglioA Bax
Oct 10, 1998·Molecular Microbiology·M Gotfredsen, K Gerdes
Mar 24, 2000·Journal of Magnetic Resonance·G ZhuK H Sze
Aug 12, 2004·Nucleic Acids Research·Lei ZhengJean-Louis Reymond
Jul 20, 2005·Biochimica Et Biophysica Acta·Sharon M KellyNicholas C Price
Sep 29, 2005·Journal of Magnetic Resonance·Donghan LeeKurt Wüthrich
Jul 25, 2006·Nature Methods·Victor JaravineVladislav Yu Orekhov
Oct 13, 2006·Bioinformatics·Stefan HoopsUrsula Kummer
Mar 19, 2009·Science Signaling·Craig R Roy, Shaeri Mukherjee
Apr 14, 2009·Molecular Cell·Carolyn A WorbyJack E Dixon
Aug 1, 2007·Journal of Applied Crystallography·Airlie J McCoyRandy J Read
Jun 9, 2009·PloS One·Lisa N KinchNick V Grishin
Jan 9, 2010·Acta Crystallographica. Section D, Biological Crystallography·Vincent B ChenDavid C Richardson
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Wolfgang Kabsch
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Paul D AdamsPeter H Zwart
Mar 6, 2010·Methods in Molecular Biology·Sina ReckelFrank Bernhard
Apr 13, 2010·Acta Crystallographica. Section D, Biological Crystallography·P EmsleyK Cowtan
Apr 23, 2010·The Journal of Biological Chemistry·Phi LuongKim Orth
Jul 14, 2010·Nature Structural & Molecular Biology·Junyu XiaoJack E Dixon
Jan 8, 2011·Protein Science : a Publication of the Protein Society·Dinesh V PalaniveluTilman Schirmer
Apr 5, 2011·Acta Crystallographica. Section D, Biological Crystallography·Garib N MurshudovAlexei A Vagin
Jul 8, 2011·Nature·Yunhao Tan, Zhao-Qing Luo
Feb 4, 2012·PLoS Biology·Joe H LevineMichael B Elowitz
Jul 1, 1995·Journal of Biomolecular NMR·C BartelsK Wüthrich
Jun 26, 2013·Acta Crystallographica. Section D, Biological Crystallography·Philip R Evans, Garib N Murshudov
Jan 24, 2014·The Journal of Biological Chemistry·Amit SundriyalTilman Schirmer
Feb 11, 2014·Trends in Biochemical Sciences·Abel Garcia-PinoRemy Loris
Dec 3, 2014·Current Biology : CB·Joe H Levine, Michael B Elowitz
Jun 4, 2015·Scientific Reports·Shradha Khater, Debasisa Mohanty
Aug 25, 2015·Cell Reports·Alexander HarmsChristoph Dehio

❮ Previous
Next ❯

Citations

Aug 3, 2016·Annual Review of Microbiology·Alexander HarmsChristoph Dehio
Mar 20, 2019·Journal of Cell Science·Ranjan SenguptaSeema Mattoo
Mar 10, 2019·Nature Communications·Simon VeyronJacqueline Cherfils
Apr 5, 2018·Pathogens and Disease·Simon VeyronJacqueline Cherfils
Sep 29, 2020·Frontiers in Microbiology·Can-Hua LuZhao-Qing Luo
Jan 12, 2020·Communications Biology·Hadas NevenzalDoron Gerber
Apr 1, 2021·Protein Science : a Publication of the Protein Society·Pieter De BruynRemy Loris
May 6, 2021·Open Biology·Bhaskar K Chatterjee, Matthias C Truttmann
Aug 19, 2017·Chemical Reviews·Amanda K Casey, Kim Orth
Oct 28, 2021·Microbial Genomics·Christopher A MullallyCharlene M Kahler

❮ Previous
Next ❯

Related Concepts

Related Feeds

Bacterial Protein Structures

Bacterial protein structures can expedite the development of novel antibiotics. Here is the latest research on bacterial proteins and the resolution of their structures.

Bacterial Protein Structures (ASM)

Bacterial protein structures can expedite the development of novel antibiotics. Here is the latest research on bacterial proteins and the resolution of their structures.

Related Papers

Nihon saikingaku zasshi. Japanese journal of bacteriology
Hideyuki Takahashi
Nihon rinsho. Japanese journal of clinical medicine
Hideyuki Takahashi, Haruo Watanabe
Bacteriologia, virusologia, parazitologia, epidemiologia
O M Dorobăţ
© 2022 Meta ULC. All rights reserved