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- EMDB-20741: Human IMPDH2 treated with ATP, IMP, and 20 mM GTP. Fully compress... -
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Basic information
Entry | Database: EMDB / ID: EMD-20741 | |||||||||
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Title | Human IMPDH2 treated with ATP, IMP, and 20 mM GTP. Fully compressed filament segment reconstruction. | |||||||||
![]() | Human IMPDH2 treated with ATP, IMP, and 20 mM GTP. Fully compressed filament segment reconstruction. | |||||||||
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![]() | metabolism / filament / allostery / adenine / guanine / BIOSYNTHETIC PROTEIN | |||||||||
Function / homology | ![]() 'de novo' XMP biosynthetic process / lymphocyte proliferation / Purine ribonucleoside monophosphate biosynthesis / IMP dehydrogenase activity / IMP dehydrogenase / GMP biosynthetic process / Azathioprine ADME / peroxisomal membrane / GTP biosynthetic process / cellular response to interleukin-4 ...'de novo' XMP biosynthetic process / lymphocyte proliferation / Purine ribonucleoside monophosphate biosynthesis / IMP dehydrogenase activity / IMP dehydrogenase / GMP biosynthetic process / Azathioprine ADME / peroxisomal membrane / GTP biosynthetic process / cellular response to interleukin-4 / circadian rhythm / secretory granule lumen / ficolin-1-rich granule lumen / Potential therapeutics for SARS / nucleotide binding / Neutrophil degranulation / DNA binding / RNA binding / extracellular exosome / extracellular region / membrane / nucleus / metal ion binding / cytosol / cytoplasm Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.21 Å | |||||||||
![]() | Johnson MC / Kollman JM | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Cryo-EM structures demonstrate human IMPDH2 filament assembly tunes allosteric regulation. Authors: Matthew C Johnson / Justin M Kollman / ![]() Abstract: Inosine monophosphate dehydrogenase (IMPDH) mediates the first committed step in guanine nucleotide biosynthesis and plays important roles in cellular proliferation and the immune response. IMPDH ...Inosine monophosphate dehydrogenase (IMPDH) mediates the first committed step in guanine nucleotide biosynthesis and plays important roles in cellular proliferation and the immune response. IMPDH reversibly polymerizes in cells and tissues in response to changes in metabolic demand. Self-assembly of metabolic enzymes is increasingly recognized as a general mechanism for regulating activity, typically by stabilizing specific conformations of an enzyme, but the regulatory role of IMPDH filaments has remained unclear. Here, we report a series of human IMPDH2 cryo-EM structures in both active and inactive conformations. The structures define the mechanism of filament assembly, and reveal how filament-dependent allosteric regulation of IMPDH2 makes the enzyme less sensitive to feedback inhibition, explaining why assembly occurs under physiological conditions that require expansion of guanine nucleotide pools. Tuning sensitivity to an allosteric inhibitor distinguishes IMPDH from other metabolic filaments, and highlights the diversity of regulatory outcomes that can emerge from self-assembly. | |||||||||
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 | ![]() | 8.5 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 18.1 KB 18.1 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 14.2 KB | Display | ![]() |
Images | ![]() | 78.6 KB | ||
Masks | ![]() | 244.1 MB | ![]() | |
Filedesc metadata | ![]() | 5.6 KB | ||
Others | ![]() ![]() | 187.7 MB 187.6 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 6udoMC ![]() 6u8eC ![]() 6u8nC ![]() 6u8rC ![]() 6u8sC ![]() 6u9oC ![]() 6ua2C ![]() 6ua4C ![]() 6ua5C ![]() 6uajC ![]() 6uc2C ![]() 6udpC ![]() 6udqC C: citing same article ( M: atomic model generated by this map |
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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
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Annotation | Human IMPDH2 treated with ATP, IMP, and 20 mM GTP. Fully compressed filament segment reconstruction. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.8265 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Mask #1
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Projections & Slices |
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Density Histograms |
-Half map: half map 2
File | emd_20741_half_map_1.map | ||||||||||||
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Annotation | half map 2 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: half map 1
File | emd_20741_half_map_2.map | ||||||||||||
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Annotation | half map 1 | ||||||||||||
Projections & Slices |
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Density Histograms |
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Sample components
-Entire : Human IMPDH2 treated with ATP, IMP, and 20 mM GTP. Filament assem...
Entire | Name: Human IMPDH2 treated with ATP, IMP, and 20 mM GTP. Filament assembly interface reconstruction. |
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Components |
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-Supramolecule #1: Human IMPDH2 treated with ATP, IMP, and 20 mM GTP. Filament assem...
Supramolecule | Name: Human IMPDH2 treated with ATP, IMP, and 20 mM GTP. Filament assembly interface reconstruction. type: organelle_or_cellular_component / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: Inosine-5'-monophosphate dehydrogenase 2
Macromolecule | Name: Inosine-5'-monophosphate dehydrogenase 2 / type: protein_or_peptide / ID: 1 / Number of copies: 16 / Enantiomer: LEVO / EC number: IMP dehydrogenase |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 56.4805 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: SEFELMADYL ISGGTSYVPD DGLTAQQLFN CGDGLTYNDF LILPGYIDFT ADQVDLTSAL TKKITLKTPL VSSPMDTVTE AGMAIAMAL TGGIGFIHHN CTPEFQANEV RKVKKYEQGF ITDPVVLSPK DRVRDVFEAK ARHGFCGIPI TDTGRMGSRL V GIISSRDI ...String: SEFELMADYL ISGGTSYVPD DGLTAQQLFN CGDGLTYNDF LILPGYIDFT ADQVDLTSAL TKKITLKTPL VSSPMDTVTE AGMAIAMAL TGGIGFIHHN CTPEFQANEV RKVKKYEQGF ITDPVVLSPK DRVRDVFEAK ARHGFCGIPI TDTGRMGSRL V GIISSRDI DFLKEEEHDC FLEEIMTKRE DLVVAPAGIT LKEANEILQR SKKGKLPIVN EDDELVAIIA RTDLKKNRDY PL ASKDAKK QLLCGAAIGT HEDDKYRLDL LAQAGVDVVV LDSSQGNSIF QINMIKYIKD KYPNLQVIGG NVVTAAQAKN LID AGVDAL RVGMGSGSIC ITQEVLACGR PQATAVYKVS EYARRFGVPV IADGGIQNVG HIAKALALGA STVMMGSLLA ATTE APGEY FFSDGIRLKK YRGMGSLDAM DKHLSSQNRY FSEADKIKVA QGVSGAVQDK GSIHKFVPYL IAGIQHSCQD IGAKS LTQV RAMMYSGELK FEKRTSSAQV EGGVHSLHSY EKRLF UniProtKB: Inosine-5'-monophosphate dehydrogenase 2 |
-Macromolecule #2: INOSINIC ACID
Macromolecule | Name: INOSINIC ACID / type: ligand / ID: 2 / Number of copies: 8 / Formula: IMP |
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Molecular weight | Theoretical: 348.206 Da |
Chemical component information | ![]() ChemComp-I: |
-Macromolecule #3: GUANOSINE-5'-TRIPHOSPHATE
Macromolecule | Name: GUANOSINE-5'-TRIPHOSPHATE / type: ligand / ID: 3 / Number of copies: 16 / Formula: GTP |
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Molecular weight | Theoretical: 523.18 Da |
Chemical component information | ![]() ChemComp-GTP: |
-Macromolecule #4: ADENOSINE-5'-TRIPHOSPHATE
Macromolecule | Name: ADENOSINE-5'-TRIPHOSPHATE / type: ligand / ID: 4 / Number of copies: 8 / Formula: ATP |
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Molecular weight | Theoretical: 507.181 Da |
Chemical component information | ![]() ChemComp-ATP: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | filament |
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Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 100.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |