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TitleM. mazei glutamine synthetase and glutamine synthetase-GlnK1 structures reveal enzyme regulation by oligomer modulation.
Journal, issue, pagesNat Commun, Vol. 14, Issue 1, Page 7375, Year 2023
Publish dateNov 15, 2023
AuthorsMaria A Schumacher / Raul Salinas / Brady A Travis / Rajiv Ranjan Singh / Nicholas Lent /
PubMed AbstractGlutamine synthetases (GS) play central roles in cellular nitrogen assimilation. Although GS active-site formation requires the oligomerization of just two GS subunits, all GS form large, multi- ...Glutamine synthetases (GS) play central roles in cellular nitrogen assimilation. Although GS active-site formation requires the oligomerization of just two GS subunits, all GS form large, multi-oligomeric machines. Here we describe a structural dissection of the archaeal Methanosarcina mazei (Mm) GS and its regulation. We show that Mm GS forms unstable dodecamers. Strikingly, we show this Mm GS oligomerization property is leveraged for a unique mode of regulation whereby labile Mm GS hexamers are stabilized by binding the nitrogen regulatory protein, GlnK1. Our GS-GlnK1 structure shows that GlnK1 functions as molecular glue to affix GS hexamers together, stabilizing formation of GS active-sites. These data, therefore, reveal the structural basis for a unique form of enzyme regulation by oligomer modulation.
External linksNat Commun / PubMed:37968329 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution2.3 - 6.9 Å
Structure data

41228

8tfb

EMDB-41228, PDB-8tfb:
Cryo-EM structure of the Methanosarcina mazei apo glutamin synthetase structure: dodecameric form
Method: EM (single particle) / Resolution: 2.99 Å

41229

8tfc

EMDB-41229, PDB-8tfc:
Cryo-EM structure of Methanosarcina mazie glutamine synthetase captured as partial oligomer
Method: EM (single particle) / Resolution: 6.9 Å

41232

8tfk

EMDB-41232, PDB-8tfk:
Cryo-EM structure of the Methanosarcina mazei glutamine synthetase (GS) with Met-Sox-P and ADP
Method: EM (single particle) / Resolution: 2.66 Å

PDB-8tge:
Crystal structure of the Methanosarcina mazei glutamine synthetase in complex with GlnK1
Method: X-RAY DIFFRACTION / Resolution: 2.3 Å

PDB-8ufj:
Structure of M. mazei GS(R167L-A168G) apo form
Method: X-RAY DIFFRACTION / Resolution: 2.45 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-P3S:
L-METHIONINE-S-SULFOXIMINE PHOSPHATE

ChemComp-ADP:
ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying molecule*YM / Adenosine diphosphate

ChemComp-HOH:
WATER / Water

Source
  • methanosarcina mazei go1 (archaea)
  • methanosarcina mazei (archaea)
KeywordsLIGASE / glutamine sythetase / GS / Methanosarcina mazei / apo / dodecamer / glutamine synthetase / partial oligomer / oligomer modulation / GS regulation / transition state / MSO / Met-Sox-P / ADP / LYASE / GlnK / PII / complex / trimer / T-loop

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