5U05

Cryo-EM structure of the E. coli CTP synthase tetramer

Summary for 5U05

• Entry DOI: 10.2210/pdb5u05/pdb
• Related: 5U03
• EMDB information: 8474 8475 8476
• Descriptor: CTP synthase (1 entity in total)
• Functional Keywords: nucleotide metabolism, enzyme, active, ligase
• Biological source: Escherichia coli
• Total number of polymer chains: 4
• Total formula weight: 241787.92

Authors

Lynch, E.M.,Hicks, D.R.,Kollman, J.M. (deposition date: 2016-11-22, release date: 2017-04-26, Last modification date: 2024-10-23)

Primary citation

Lynch, E.M.,Hicks, D.R.,Shepherd, M.,Endrizzi, J.A.,Maker, A.,Hansen, J.M.,Barry, R.M.,Gitai, Z.,Baldwin, E.P.,Kollman, J.M.
Human CTP synthase filament structure reveals the active enzyme conformation.
Nat. Struct. Mol. Biol., 24:507-514, 2017

PubMed Abstract: The universally conserved enzyme CTP synthase (CTPS) forms filaments in bacteria and eukaryotes. In bacteria, polymerization inhibits CTPS activity and is required for nucleotide homeostasis. Here we show that for human CTPS, polymerization increases catalytic activity. The cryo-EM structures of bacterial and human CTPS filaments differ considerably in overall architecture and in the conformation of the CTPS protomer, explaining the divergent consequences of polymerization on activity. The structure of human CTPS filament, the first structure of the full-length human enzyme, reveals a novel active conformation. The filament structures elucidate allosteric mechanisms of assembly and regulation that rely on a conserved conformational equilibrium. The findings may provide a mechanism for increasing human CTPS activity in response to metabolic state and challenge the assumption that metabolic filaments are generally storage forms of inactive enzymes. Allosteric regulation of CTPS polymerization by ligands likely represents a fundamental mechanism underlying assembly of other metabolic filaments.

PubMed: 28459447
DOI: 10.1038/nsmb.3407

Experimental method

ELECTRON MICROSCOPY (7.9 Å)