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- EMDB-37383: The cryo-EM structure of human sphingomyelin synthase-related pro... -
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Open data
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Basic information
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Title | The cryo-EM structure of human sphingomyelin synthase-related protein in complex with ceramide/phosphoethanolamine | |||||||||
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![]() | synthase / sphingomyelin / CPE / membrane protein / lipid metabolism | |||||||||
Function / homology | ![]() ceramide phosphoethanolamine biosynthetic process / ceramide phosphoethanolamine synthase activity / sphingomyelin synthase activity / ceramide cholinephosphotransferase activity / regulation of ceramide biosynthetic process / Transferases; Transferring phosphorus-containing groups; Transferases for other substituted phosphate groups / sphingomyelin biosynthetic process / Sphingolipid de novo biosynthesis / ceramide biosynthetic process / Golgi membrane ...ceramide phosphoethanolamine biosynthetic process / ceramide phosphoethanolamine synthase activity / sphingomyelin synthase activity / ceramide cholinephosphotransferase activity / regulation of ceramide biosynthetic process / Transferases; Transferring phosphorus-containing groups; Transferases for other substituted phosphate groups / sphingomyelin biosynthetic process / Sphingolipid de novo biosynthesis / ceramide biosynthetic process / Golgi membrane / endoplasmic reticulum membrane / endoplasmic reticulum / membrane / plasma membrane / cytosol Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.74 Å | |||||||||
![]() | Hu K / Zhang Q / Chen Y / Yao D / Zhou L / Cao Y | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Cryo-EM structure of human sphingomyelin synthase and its mechanistic implications for sphingomyelin synthesis. Authors: Kexin Hu / Qing Zhang / Yang Chen / Jintong Yang / Ying Xia / Bing Rao / Shaobai Li / Yafeng Shen / Mi Cao / Hongliang Lu / An Qin / Xian-Cheng Jiang / Deqiang Yao / Jie Zhao / Lu Zhou / Yu Cao / ![]() ![]() Abstract: Sphingomyelin (SM) has key roles in modulating mammalian membrane properties and serves as an important pool for bioactive molecules. SM biosynthesis is mediated by the sphingomyelin synthase (SMS) ...Sphingomyelin (SM) has key roles in modulating mammalian membrane properties and serves as an important pool for bioactive molecules. SM biosynthesis is mediated by the sphingomyelin synthase (SMS) family, comprising SMS1, SMS2 and SMS-related (SMSr) members. Although SMS1 and SMS2 exhibit SMS activity, SMSr possesses ceramide phosphoethanolamine synthase activity. Here we determined the cryo-electron microscopic structures of human SMSr in complexes with ceramide, diacylglycerol/phosphoethanolamine and ceramide/phosphoethanolamine (CPE). The structures revealed a hexameric arrangement with a reaction chamber located between the transmembrane helices. Within this structure, a catalytic pentad E-H/D-H-D was identified, situated at the interface between the lipophilic and hydrophilic segments of the reaction chamber. Additionally, the study unveiled the two-step synthesis process catalyzed by SMSr, involving PE-PLC (phosphatidylethanolamine-phospholipase C) hydrolysis and the subsequent transfer of the phosphoethanolamine moiety to ceramide. This research provides insights into the catalytic mechanism of SMSr and expands our understanding of sphingolipid metabolism. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 93.2 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 14.8 KB 14.8 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 9.8 KB | Display | ![]() |
Images | ![]() | 89.6 KB | ||
Filedesc metadata | ![]() | 5.5 KB | ||
Others | ![]() ![]() | 91.4 MB 91.4 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8w9wMC ![]() 8ijqC ![]() 8ijrC ![]() 8w9yC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Map
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Voxel size | X=Y=Z: 1.1 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_37383_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_37383_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
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Sample components
-Entire : The cryo-EM structure of human sphingomyelin synthase-related pro...
Entire | Name: The cryo-EM structure of human sphingomyelin synthase-related protein in complex with ceramide/phosphoethanolamine |
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Components |
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-Supramolecule #1: The cryo-EM structure of human sphingomyelin synthase-related pro...
Supramolecule | Name: The cryo-EM structure of human sphingomyelin synthase-related protein in complex with ceramide/phosphoethanolamine type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: Sphingomyelin synthase-related protein 1
Macromolecule | Name: Sphingomyelin synthase-related protein 1 / type: protein_or_peptide / ID: 1 / Number of copies: 6 / Enantiomer: LEVO / EC number: sphingomyelin synthase |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 31.056529 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: RLDPEYWKTI LSCIYVFIVF GFTSFIMVIV HERVPDMQTY PPLPDIFLDS VPRIPWAFAM TEVCGMILCY IWLLVLLLHK HRSILLRRL CSLMGTVFLL RCFTMFVTSL SVPGQHLQCT GKIYGSVWEK LHRAFAIWSG FGMTLTGVHT CGDYMFSGHT V VLTMLNFF ...String: RLDPEYWKTI LSCIYVFIVF GFTSFIMVIV HERVPDMQTY PPLPDIFLDS VPRIPWAFAM TEVCGMILCY IWLLVLLLHK HRSILLRRL CSLMGTVFLL RCFTMFVTSL SVPGQHLQCT GKIYGSVWEK LHRAFAIWSG FGMTLTGVHT CGDYMFSGHT V VLTMLNFF VTEYTPRSWN FLHTLSWVLN LFGIFFILAA HEHYSIDVFI AFYITTRLFL YYHTLANTRA YQQSRRARIW FP MFSFFEC NVNGTVPNEY CWPFSKP UniProtKB: Sphingomyelin synthase-related protein 1 |
-Macromolecule #2: ~{N}-[(~{Z},2~{S},3~{R})-1,3-bis(oxidanyl)heptadec-4-en-2-yl]dode...
Macromolecule | Name: ~{N}-[(~{Z},2~{S},3~{R})-1,3-bis(oxidanyl)heptadec-4-en-2-yl]dodecanamide type: ligand / ID: 2 / Number of copies: 6 / Formula: UJO |
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Molecular weight | Theoretical: 467.768 Da |
-Macromolecule #3: PHOSPHORIC ACID MONO-(2-AMINO-ETHYL) ESTER
Macromolecule | Name: PHOSPHORIC ACID MONO-(2-AMINO-ETHYL) ESTER / type: ligand / ID: 3 / Number of copies: 4 / Formula: OPE |
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Molecular weight | Theoretical: 141.063 Da |
Chemical component information | ![]() ChemComp-OPE: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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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 K3 (6k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: SPOT SCAN / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.6 µm / Nominal defocus min: 1.0 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |