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- EMDB-30599: Cryo-EM structures of human GMPPA/GMPPB complex bound to GDP-Mannose -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-30599 | |||||||||
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Title | Cryo-EM structures of human GMPPA/GMPPB complex bound to GDP-Mannose | |||||||||
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Function / homology | ![]() mannose-1-phosphate guanylyltransferase / mannose-1-phosphate guanylyltransferase (GTP) activity / Synthesis of GDP-mannose / GDP-mannose biosynthetic process / biosynthetic process / protein glycosylation / transferase activity / GTP binding / extracellular exosome / cytoplasm Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / negative staining / Resolution: 3.4 Å | |||||||||
![]() | Zheng L / Liu Z / Wang Y / Yang F / Wang J / Qing J / Cai X / Mo X / Gao N / Jia D | |||||||||
Funding support | 1 items
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![]() | ![]() Title: Cryo-EM structures of human GMPPA-GMPPB complex reveal how cells maintain GDP-mannose homeostasis. Authors: Lvqin Zheng / Zhe Liu / Yan Wang / Fan Yang / Jinrui Wang / Wenjie Huang / Jiao Qin / Min Tian / Xiaotang Cai / Xiaohui Liu / Xianming Mo / Ning Gao / Da Jia / ![]() Abstract: GDP-mannose (GDP-Man) is a key metabolite essential for protein glycosylation and glycophosphatidylinositol anchor synthesis, and aberrant cellular GDP-Man levels have been associated with multiple ...GDP-mannose (GDP-Man) is a key metabolite essential for protein glycosylation and glycophosphatidylinositol anchor synthesis, and aberrant cellular GDP-Man levels have been associated with multiple human diseases. How cells maintain homeostasis of GDP-Man is unknown. Here, we report the cryo-EM structures of human GMPPA-GMPPB complex, the protein machinery responsible for GDP-Man synthesis, in complex with GDP-Man or GTP. Unexpectedly, we find that the catalytically inactive subunit GMPPA displays a much higher affinity to GDP-Man than the active subunit GMPPB and, subsequently, inhibits the catalytic activity of GMPPB through a unique C-terminal loop of GMPPA. Importantly, disruption of the interactions between GMPPA and GMPPB or the binding of GDP-Man to GMPPA in zebrafish leads to abnormal brain development and muscle abnormality, analogous to phenotypes observed in individuals carrying GMPPA or GMPPB mutations. We conclude that GMPPA acts as a cellular sensor to maintain mannose homeostasis through allosterically regulating GMPPB. | |||||||||
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 | ![]() | 48.8 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 12.3 KB 12.3 KB | Display Display | ![]() |
Images | ![]() | 66.3 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 492.7 KB | Display | ![]() |
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Full document | ![]() | 492.3 KB | Display | |
Data in XML | ![]() | 6 KB | Display | |
Data in CIF | ![]() | 6.8 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7d72MC ![]() 7d73C ![]() 7d74C 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
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Voxel size | X=Y=Z: 1.057 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 : GMPPA/GMPPB complex
Entire | Name: GMPPA/GMPPB complex |
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Components |
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-Supramolecule #1: GMPPA/GMPPB complex
Supramolecule | Name: GMPPA/GMPPB complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: ![]() |
Recombinant expression | Organism: ![]() |
-Macromolecule #1: Mannose-1-phosphate guanyltransferase beta
Macromolecule | Name: Mannose-1-phosphate guanyltransferase beta / type: protein_or_peptide / ID: 1 / Number of copies: 8 / Enantiomer: LEVO / EC number: mannose-1-phosphate guanylyltransferase |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 39.878316 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MKALILVGGY GTRLRPLTLS TPKPLVDFCN KPILLHQVEA LAAAGVDHVI LAVSYMSQVL EKEMKAQEQR LGIRISMSHE EEPLGTAGP LALARDLLSE TADPFFVLNS DVICDFPFQA MVQFHRHHGQ EGSILVTKVE EPSKYGVVVC EADTGRIHRF V EKPQVFVS ...String: MKALILVGGY GTRLRPLTLS TPKPLVDFCN KPILLHQVEA LAAAGVDHVI LAVSYMSQVL EKEMKAQEQR LGIRISMSHE EEPLGTAGP LALARDLLSE TADPFFVLNS DVICDFPFQA MVQFHRHHGQ EGSILVTKVE EPSKYGVVVC EADTGRIHRF V EKPQVFVS NKINAGMYIL SPAVLQRIQL QPTSIEKEVF PIMAKEGQLY AMELQGFWMD IGQPKDFLTG MCLFLQSLRQ KQ PERLCSG PGIVGNVLVD PSARIGQNCS IGPNVSLGPG VVVEDGVCIR RCTVLRDARI RSHSWLESCI VGWRCRVGQW VRM ENVTVL GEDVIVNDEL YLNGASVLPH KSIGESVPEP RIIM |
-Macromolecule #2: Mannose-1-phosphate guanyltransferase alpha
Macromolecule | Name: Mannose-1-phosphate guanyltransferase alpha / type: protein_or_peptide / ID: 2 / Number of copies: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 46.341961 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MLKAVILIGG PQKGTRFRPL SFEVPKPLFP VAGVPMIQHH IEACAQVPGM QEILLIGFYQ PDEPLTQFLE AAQQEFNLPV RYLQEFAPL GTGGGLYHFR DQILAGSPEA FFVLNADVCS DFPLSAMLEA HRRQRHPFLL LGTTANRTQS LNYGCIVENP Q THEVLHYV ...String: MLKAVILIGG PQKGTRFRPL SFEVPKPLFP VAGVPMIQHH IEACAQVPGM QEILLIGFYQ PDEPLTQFLE AAQQEFNLPV RYLQEFAPL GTGGGLYHFR DQILAGSPEA FFVLNADVCS DFPLSAMLEA HRRQRHPFLL LGTTANRTQS LNYGCIVENP Q THEVLHYV EKPSTFISDI INCGIYLFSP EALKPLRDVF QRNQQDGQLE DSPGLWPGAG TIRLEQDVFS ALAGQGQIYV HL TDGIWSQ IKSAGSALYA SRLYLSRYQD THPERLAKHT PGGPWIRGNV YIHPTAKVAP SAVLGPNVSI GKGVTVGEGV RLR ESIVLH GATLQEHTCV LHSIVGWGST VGRWARVEGT PSDPNPNDPR ARMDSESLFK DGKLLPAITI LGCRVRIPAE VLIL NSIVL PHKELSRSFT NQIIL |
-Macromolecule #3: GUANOSINE-5'-DIPHOSPHATE-ALPHA-D-MANNOSE
Macromolecule | Name: GUANOSINE-5'-DIPHOSPHATE-ALPHA-D-MANNOSE / type: ligand / ID: 3 / Number of copies: 12 / Formula: GDD |
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Molecular weight | Theoretical: 605.341 Da |
Chemical component information | ![]() ChemComp-GDD: |
-Macromolecule #4: MAGNESIUM ION
Macromolecule | Name: MAGNESIUM ION / type: ligand / ID: 4 / Number of copies: 3 / Formula: MG |
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Molecular weight | Theoretical: 24.305 Da |
-Macromolecule #5: water
Macromolecule | Name: water / type: ligand / ID: 5 / Number of copies: 6 / Formula: HOH |
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Molecular weight | Theoretical: 18.015 Da |
Chemical component information | ![]() ChemComp-HOH: |
-Experimental details
-Structure determination
Method | negative staining, cryo EM |
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![]() | single particle reconstruction |
Aggregation state | cell |
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Sample preparation
Buffer | pH: 8 |
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Staining | Type: NEGATIVE / Material: Uranyl Acetate |
Vitrification | Cryogen name: NITROGEN |
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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: 64.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: SPOT SCAN / Imaging mode: DARK FIELD |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.4 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 57299 |
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Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |