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- EMDB-20354: cryoEM structure of the substrate-bound human CTP synthase 2 filament -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-20354 | |||||||||
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Title | cryoEM structure of the substrate-bound human CTP synthase 2 filament | |||||||||
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Function / homology | ![]() CTP synthase (glutamine hydrolysing) / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | ![]() ![]() | |||||||||
![]() | Lynch EM / Kollman JM | |||||||||
![]() | ![]() Title: Coupled structural transitions enable highly cooperative regulation of human CTPS2 filaments. Authors: Eric M Lynch / Justin M Kollman / ![]() Abstract: Many enzymes assemble into defined oligomers, providing a mechanism for cooperatively regulating activity. Recent studies have described a mode of regulation in which enzyme activity is modulated by ...Many enzymes assemble into defined oligomers, providing a mechanism for cooperatively regulating activity. Recent studies have described a mode of regulation in which enzyme activity is modulated by polymerization into large-scale filaments. Here we describe an ultrasensitive form of polymerization-based regulation employed by human CTP synthase 2 (CTPS2). Cryo-EM structures reveal that CTPS2 filaments dynamically switch between active and inactive forms in response to changes in substrate and product levels. Linking the conformational state of many CTPS2 subunits in a filament results in highly cooperative regulation, greatly exceeding the limits of cooperativity for the CTPS2 tetramer alone. The structures reveal a link between conformation and control of ammonia channeling between the enzyme's active sites, and explain differences in regulation of human CTPS isoforms. This filament-based mechanism of enhanced cooperativity demonstrates how the widespread phenomenon of enzyme polymerization can be adapted to achieve different regulatory outcomes. | |||||||||
History |
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Structure visualization
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 95.7 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 10.1 KB 10.1 KB | Display Display | ![]() |
Images | ![]() | 245.4 KB | ||
Filedesc metadata | ![]() | 5.2 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 6pk4MC ![]() 6pk7C M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
File | ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Voxel size | X=Y=Z: 1.05 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
-Entire : substrate-bound CTP synthase 2 filament
Entire | Name: substrate-bound CTP synthase 2 filament |
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Components |
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-Supramolecule #1: substrate-bound CTP synthase 2 filament
Supramolecule | Name: substrate-bound CTP synthase 2 filament / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() ![]() |
-Macromolecule #1: CTP synthase 2
Macromolecule | Name: CTP synthase 2 / type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO / EC number: CTP synthase (glutamine hydrolysing) |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 65.75943 KDa |
Recombinant expression | Organism: ![]() ![]() ![]() |
Sequence | String: MKYILVTGGV ISGIGKGIIA SSIGTILKSC GLRVTAIKID PYINIDAGTF SPYEHGEVFV LNDGGEVDLD LGNYERFLDI NLYKDNNIT TGKIYQHVIN KERRGDYLGK TVQVVPHITD AVQEWVMNQA KVPVDGNKEE PQICVIELGG TIGDIEGMPF V EAFRQFQF ...String: MKYILVTGGV ISGIGKGIIA SSIGTILKSC GLRVTAIKID PYINIDAGTF SPYEHGEVFV LNDGGEVDLD LGNYERFLDI NLYKDNNIT TGKIYQHVIN KERRGDYLGK TVQVVPHITD AVQEWVMNQA KVPVDGNKEE PQICVIELGG TIGDIEGMPF V EAFRQFQF KAKRENFCNI HVSLVPQLSA TGEQKTKPTQ NSVRALRGLG LSPDLIVCRS STPIEMAVKE KISMFCHVNP EQ VICIHDV SSTYRVPVLL EEQSIVKYFK ERLHLPIGDS ASNLLFKWRN MADRYERLQK ICSIALVGKY TKLRDCYASV FKA LEHSAL AINHKLNLMY IDSIDLEKIT ETEDPVKFHE AWQKLCKADG ILVPGGFGIR GTLGKLQAIS WARTKKIPFL GVCL GMQLA VIEFARNCLN LKDADSTEFR PNAPVPLVID MPEHNPGNLG GTMRLGIRRT VFKTENSILR KLYGDVPFIE ERHRH RFEV NPNLIKQFEQ NDLSFVGQDV DGDRMEIIEL ANHPYFVGVQ FHPEFSSRPM KPSPPYLGLL LAATGNLNAY LQQGCK LSS SDRYSDASDD SFSEPRIAEL EIS UniProtKB: ![]() |
-Macromolecule #2: URIDINE 5'-TRIPHOSPHATE
Macromolecule | Name: URIDINE 5'-TRIPHOSPHATE / type: ligand / ID: 2 / Number of copies: 4 / Formula: UTP |
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Molecular weight | Theoretical: 484.141 Da |
Chemical component information | ![]() ChemComp-UTP: |
-Macromolecule #3: ADENOSINE-5'-TRIPHOSPHATE
Macromolecule | Name: ADENOSINE-5'-TRIPHOSPHATE / type: ligand / ID: 3 / Number of copies: 4 / Formula: ATP |
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Molecular weight | Theoretical: 507.181 Da |
Chemical component information | ![]() ChemComp-ATP: |
-Experimental details
-Structure determination
Method | ![]() |
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Aggregation state | filament |
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Sample preparation
Buffer | pH: 7.9 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD![]() |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: SUPER-RESOLUTION / Average electron dose: 90.0 e/Å2 |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Startup model | Type of model: INSILICO MODEL |
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Initial angle assignment | Type: MAXIMUM LIKELIHOOD / Software - Name: RELION |
Final angle assignment | Type: MAXIMUM LIKELIHOOD / Software - Name: cisTEM |
Final reconstruction | Applied symmetry - Point group: D2 (2x2 fold dihedral![]() |