|Entry||Database: EMDB / ID: 8476|
|Title||human CTP synthase 1 - mutant H355A|
|Map data||human CTP synthase 1 - mutant H355A|
|Function/homology||CTP synthase / CTP synthase activity / CTP synthase GATase domain / CTP synthase, N-terminal / CTP synthase / CTP synthase N-terminus / 'de novo' CTP biosynthetic process / Glutamine amidotransferase / Glutamine amidotransferase type 1 domain profile. / B cell proliferation ...CTP synthase / CTP synthase activity / CTP synthase GATase domain / CTP synthase, N-terminal / CTP synthase / CTP synthase N-terminus / 'de novo' CTP biosynthetic process / Glutamine amidotransferase / Glutamine amidotransferase type 1 domain profile. / B cell proliferation / CTP biosynthetic process / Glutamine amidotransferase class-I / nucleobase-containing compound metabolic process / Interconversion of nucleotide di- and triphosphates / glutamine metabolic process / T cell proliferation / nucleobase-containing small molecule interconversion / Class I glutamine amidotransferase-like / response to drug / P-loop containing nucleoside triphosphate hydrolase / membrane / ATP binding / identical protein binding / cytosol / | / CTP synthase 1|
Function and homology information
|Source||Homo sapiens / / human|
|Method||single particle reconstruction / 17 Å resolution|
|Authors||Lynch EM / Kollman JM|
|Citation||Journal: Nat. Struct. Mol. Biol. / Year: 2017|
Title: Human CTP synthase filament structure reveals the active enzyme conformation.
Authors: Eric M Lynch / Derrick R Hicks / Matthew Shepherd / James A Endrizzi / Allison Maker / Jesse M Hansen / Rachael M Barry / Zemer Gitai / Enoch P Baldwin / Justin M Kollman
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 ...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.
|Date||Deposition: Nov 22, 2016 / Header (metadata) release: Feb 8, 2017 / Map release: Apr 26, 2017 / Last update: Jun 21, 2017|
Downloads & links
|File||emd_8476.map.gz (map file in CCP4 format, 5620 KB)|
|Projections & slices|
Images are generated by Spider package.
|Voxel size||X=Y=Z: 2.07 Å|
CCP4 map header:
-Entire hCTPS1-H355A tetramer
|Entire||Name: hCTPS1-H355A tetramer / Number of components: 2|
-Component #1: protein, hCTPS1-H355A tetramer
|Protein||Name: hCTPS1-H355A tetramer / Recombinant expression: No|
|Source||Species: Homo sapiens / / human|
|Source (engineered)||Expression System: Saccharomyces cerevisiae / / yeast / / Vector: pDO105-hCTPS1-H355A|
-Component #2: protein, hCTPS1-H355A
|Protein||Name: hCTPS1-H355A / Recombinant expression: No|
|Source (engineered)||Expression System: Homo sapiens / / human|
|Specimen||Specimen state: particle|
|Sample solution||pH: 7.9|
|Vitrification||Cryogen name: NONE|
-Electron microscopy imaging
Model: Tecnai Spirit / Image courtesy: FEI Company
|Imaging||Microscope: FEI TECNAI SPIRIT|
|Electron gun||Electron source: FIELD EMISSION GUN / Accelerating voltage: 120 kV / Electron dose: 40 e/Å2 / Illumination mode: OTHER|
|Lens||Imaging mode: BRIGHT FIELD|
|Specimen Holder||Model: OTHER|
|Camera||Detector: GATAN ULTRASCAN 4000 (4k x 4k)|
|Processing||Method: single particle reconstruction / Applied symmetry: D2 (2*2 fold dihedral) / Number of projections: 4413|
|3D reconstruction||Software: RELION / Resolution: 17 Å / Resolution method: FSC 0.143 CUT-OFF|
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