The content discusses the regulation of glutamine synthetase (GS) activity in the methanogenic archaeon Methanosarcina mazei. Key insights are:
The metabolite 2-oxoglutarate (2-OG) is the central regulator of M. mazei GS (GlnA1) activity. 2-OG triggers the assembly of GlnA1 into an active dodecameric complex, without any detectable intermediate oligomeric states.
The binding of 2-OG at the interface between two GlnA1 protomers acts as a "molecular glue", facilitating the cooperative dodecamer assembly. Additionally, 2-OG induces a conformational change in the active site, priming it for catalysis.
The presence of the PII-like protein GlnK1 does not affect GlnA1 dodecamer assembly or activity under the tested conditions, contrary to previous reports suggesting GlnK1 stabilizes the dodecameric structure.
GlnA1 is feedback inhibited by glutamine, with the conserved arginine residue R66 playing a key role in this regulation. However, glutamine does not induce disassembly of the dodecameric complex.
The direct 2-OG activation and glutamine feedback inhibition represent unique regulatory mechanisms for M. mazei GS, distinct from the regulation observed in other bacteria and eukaryotes.
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by Herdering,E.... på www.biorxiv.org 03-19-2024
https://www.biorxiv.org/content/10.1101/2024.03.18.585516v1Djupare frågor