English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

Differences in regulation mechanisms of glutamine synthetases from methanogenic archaea unveiled by structural investigations

MPS-Authors
/persons/resource/persons257446

Müller,  Marie-Caroline
Research Group Microbial Metabolism, Max Planck Institute for Marine Microbiology, Max Planck Society;

/persons/resource/persons256577

Lemaire,  Olivier N.
Research Group Microbial Metabolism, Max Planck Institute for Marine Microbiology, Max Planck Society;

/persons/resource/persons256582

Wagner,  Tristan
Research Group Microbial Metabolism, Max Planck Institute for Marine Microbiology, Max Planck Society;

External Resource
No external resources are shared
Fulltext (restricted access)
There are currently no full texts shared for your IP range.
Fulltext (public)

42003_2023_Article_5726.pdf
(Publisher version), 5MB

Supplementary Material (public)
There is no public supplementary material available
Citation

Müller, M.-C., Lemaire, O. N., Kurth, J. M., Welte, C. U., & Wagner, T. (2024). Differences in regulation mechanisms of glutamine synthetases from methanogenic archaea unveiled by structural investigations. Communications Biology. doi:10.1038/s42003-023-05726-w.


Cite as: https://hdl.handle.net/21.11116/0000-000E-4949-F
Abstract
Glutamine synthetases (GS) catalyze the ATP-dependent ammonium assimilation, the initial step of nitrogen acquisition that must be under tight control to fit cellular needs. While their catalytic mechanisms and regulations are well-characterized in bacteria and eukaryotes, only limited knowledge exists in archaea. Here, we solved two archaeal GS structures and unveiled unexpected differences in their regulatory mechanisms. GS from Methanothermococcus thermolithotrophicus is inactive in its resting state and switched on by 2-oxoglutarate, a sensor of cellular nitrogen deficiency. The enzyme activation overlays remarkably well with the reported cellular concentration for 2-oxoglutarate. Its binding to an allosteric pocket reconfigures the active site through long-range conformational changes. The homolog from Methermicoccus shengliensis does not harbor the 2-oxoglutarate binding motif and, consequently, is 2-oxoglutarate insensitive. Instead, it is directly feedback-inhibited through glutamine recognition by the catalytic Asp50'-loop, a mechanism common to bacterial homologs, but absent in M. thermolithotrophicus due to residue substitution. Analyses of residue conservation in archaeal GS suggest that both regulations are widespread and not mutually exclusive. While the effectors and their binding sites are surprisingly different, the molecular mechanisms underlying their mode of action on GS activity operate on the same molecular determinants in the active site.