[English] 日本語
![](img/lk-miru.gif)
- EMDB-22606: Human serine palmitoyltransferase complex SPTLC1/SPLTC2/ssSPTa/OR... -
+
Open data
-
Basic information
Entry | Database: EMDB / ID: EMD-22606 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | Human serine palmitoyltransferase complex SPTLC1/SPLTC2/ssSPTa/ORMDL3, class 4 | |||||||||
![]() | Sharpened_map | |||||||||
![]() |
| |||||||||
Function / homology | ![]() negative regulation of ceramide biosynthetic process / sphinganine biosynthetic process / regulation of fat cell apoptotic process / sphingomyelin biosynthetic process / serine palmitoyltransferase complex / intracellular sphingolipid homeostasis / : / serine C-palmitoyltransferase activity / serine C-palmitoyltransferase / ceramide metabolic process ...negative regulation of ceramide biosynthetic process / sphinganine biosynthetic process / regulation of fat cell apoptotic process / sphingomyelin biosynthetic process / serine palmitoyltransferase complex / intracellular sphingolipid homeostasis / : / serine C-palmitoyltransferase activity / serine C-palmitoyltransferase / ceramide metabolic process / regulation of smooth muscle contraction / sphingosine biosynthetic process / sphingolipid biosynthetic process / Sphingolipid de novo biosynthesis / sphingolipid metabolic process / ceramide biosynthetic process / negative regulation of B cell apoptotic process / motor behavior / positive regulation of lipophagy / adipose tissue development / positive regulation of autophagy / specific granule membrane / myelination / secretory granule membrane / protein localization / positive regulation of protein localization to nucleus / pyridoxal phosphate binding / Neutrophil degranulation / endoplasmic reticulum membrane / endoplasmic reticulum / plasma membrane Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.1 Å | |||||||||
![]() | Wang Y / Niu Y / Zhang Z / Zhao H / Myasnikov A / Kalathur R / Lee CH | |||||||||
![]() | ![]() Title: Structural insights into the regulation of human serine palmitoyltransferase complexes. Authors: Yingdi Wang / Yiming Niu / Zhe Zhang / Kenneth Gable / Sita D Gupta / Niranjanakumari Somashekarappa / Gongshe Han / Hongtu Zhao / Alexander G Myasnikov / Ravi C Kalathur / Teresa M Dunn / Chia-Hsueh Lee / ![]() ![]() Abstract: Sphingolipids are essential lipids in eukaryotic membranes. In humans, the first and rate-limiting step of sphingolipid synthesis is catalyzed by the serine palmitoyltransferase holocomplex, which ...Sphingolipids are essential lipids in eukaryotic membranes. In humans, the first and rate-limiting step of sphingolipid synthesis is catalyzed by the serine palmitoyltransferase holocomplex, which consists of catalytic components (SPTLC1 and SPTLC2) and regulatory components (ssSPTa and ORMDL3). However, the assembly, substrate processing and regulation of the complex are unclear. Here, we present 8 cryo-electron microscopy structures of the human serine palmitoyltransferase holocomplex in various functional states at resolutions of 2.6-3.4 Å. The structures reveal not only how catalytic components recognize the substrate, but also how regulatory components modulate the substrate-binding tunnel to control enzyme activity: ssSPTa engages SPTLC2 and shapes the tunnel to determine substrate specificity. ORMDL3 blocks the tunnel and competes with substrate binding through its amino terminus. These findings provide mechanistic insights into sphingolipid biogenesis governed by the serine palmitoyltransferase complex. | |||||||||
History |
|
-
Structure visualization
Movie |
![]() |
---|---|
Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
-
Downloads & links
-EMDB archive
Map data | ![]() | 157.2 MB | ![]() | |
---|---|---|---|---|
Header (meta data) | ![]() ![]() | 13.6 KB 13.6 KB | Display Display | ![]() |
Images | ![]() | 67.2 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 455.3 KB | Display | ![]() |
---|---|---|---|---|
Full document | ![]() | 454.9 KB | Display | |
Data in XML | ![]() | 6.9 KB | Display | |
Data in CIF | ![]() | 7.9 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7k0pMC ![]() 7k0iC ![]() 7k0jC ![]() 7k0kC ![]() 7k0lC ![]() 7k0mC ![]() 7k0nC ![]() 7k0oC ![]() 7k0qC M: atomic model generated by this map C: citing same article ( |
---|---|
Similar structure data |
-
Links
EMDB pages | ![]() ![]() |
---|
-
Map
File | ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Sharpened_map | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.005 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
|
-Supplemental data
-
Sample components
-Entire : human serine palmitoyltransferase complexes
Entire | Name: human serine palmitoyltransferase complexes |
---|---|
Components |
|
-Supramolecule #1: human serine palmitoyltransferase complexes
Supramolecule | Name: human serine palmitoyltransferase complexes / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
---|---|
Source (natural) | Organism: ![]() |
Recombinant expression | Organism: ![]() |
-Macromolecule #1: Serine palmitoyltransferase 1
Macromolecule | Name: Serine palmitoyltransferase 1 / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO / EC number: serine C-palmitoyltransferase |
---|---|
Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 52.80677 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MATATEQWVL VEMVQALYEA PAYHLILEGI LILWIIRLLF SKTYKLQERS DLTVKEKEEL IEEWQPEPLV PPVPKDHPAL NYNIVSGPP SHKTVVNGKE CINFASFNFL GLLDNPRVKA AALASLKKYG VGTCGPRGFY GTFDVHLDLE DRLAKFMKTE E AIIYSYGF ...String: MATATEQWVL VEMVQALYEA PAYHLILEGI LILWIIRLLF SKTYKLQERS DLTVKEKEEL IEEWQPEPLV PPVPKDHPAL NYNIVSGPP SHKTVVNGKE CINFASFNFL GLLDNPRVKA AALASLKKYG VGTCGPRGFY GTFDVHLDLE DRLAKFMKTE E AIIYSYGF ATIASAIPAY SKRGDIVFVD RAACFAIQKG LQASRSDIKL FKHNDMADLE RLLKEQEIED QKNPRKARVT RR FIVVEGL YMNTGTICPL PELVKLKYKY KARIFLEESL SFGVLGEHGR GVTEHYGINI DDIDLISANM ENALASIGGF CCG RSFVID HQRLSGQGYC FSASLPPLLA AAAIEALNIM EENPGIFAVL KEKCGQIHKA LQGISGLKVV GESLSPAFHL QLEE STGSR EQDVRLLQEI VDQCMNRSIA LTQARYLEKE EKCLPPPSIR VVVTVEQTEE ELERAASTIK EVAQAVLL |
-Macromolecule #2: Serine palmitoyltransferase 2
Macromolecule | Name: Serine palmitoyltransferase 2 / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO / EC number: serine C-palmitoyltransferase |
---|---|
Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 60.851902 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MRPEPGGCCC RRTVRANGCV ANGEVRNGYV RSSAAAAAAA AAGQIHHVTQ NGGLYKRPFN EAFEETPMLV AVLTYVGYGV LTLFGYLRD FLRYWRIEKC HHATEREEQK DFVSLYQDFE NFYTRNLYMR IRDNWNRPIC SVPGARVDIM ERQSHDYNWS F KYTGNIIK ...String: MRPEPGGCCC RRTVRANGCV ANGEVRNGYV RSSAAAAAAA AAGQIHHVTQ NGGLYKRPFN EAFEETPMLV AVLTYVGYGV LTLFGYLRD FLRYWRIEKC HHATEREEQK DFVSLYQDFE NFYTRNLYMR IRDNWNRPIC SVPGARVDIM ERQSHDYNWS F KYTGNIIK GVINMGSYNY LGFARNTGSC QEAAAKVLEE YGAGVCSTRQ EIGNLDKHEE LEELVARFLG VEAAMAYGMG FA TNSMNIP ALVGKGCLIL SDELNHASLV LGARLSGATI RIFKHNNMQS LEKLLKDAIV YGQPRTRRPW KKILILVEGI YSM EGSIVR LPEVIALKKK YKAYLYLDEA HSIGALGPTG RGVVEYFGLD PEDVDVMMGT FTKSFGASGG YIGGKKELID YLRT HSHSA VYATSLSPPV VEQIITSMKC IMGQDGTSLG KECVQQLAEN TRYFRRRLKE MGFIIYGNED SPVVPLMLYM PAKIG AFGR EMLKRNIGVV VVGFPATPII ESRARFCLSA AHTKEILDTA LKEIDEVGDL LQLKYSRHRL |
-Macromolecule #3: Serine palmitoyltransferase small subunit A
Macromolecule | Name: Serine palmitoyltransferase small subunit A / type: protein_or_peptide / ID: 3 / Number of copies: 2 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 8.471095 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MAGMALARAW KQMSWFYYQY LLVTALYMLE PWERTVFNSM LVSIVGMALY TGYVFMPQHI MAILHYFEIV Q |
-Macromolecule #4: ORM1-like protein 3
Macromolecule | Name: ORM1-like protein 3 / type: protein_or_peptide / ID: 4 / Number of copies: 2 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 17.512594 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MNVGTAHSEV NPNTRVMNSR GIWLSYVLAI GLLHIVLLSI PFVSVPVVWT LTNLIHNMGM YIFLHTVKGT PFETPDQGKA RLLTHWEQM DYGVQFTASR KFLTITPIVL YFLTSFYTKY DQIHFVLNTV SLMSVLIPKL PQLHGVRIFG INKY |
-Macromolecule #5: PYRIDOXAL-5'-PHOSPHATE
Macromolecule | Name: PYRIDOXAL-5'-PHOSPHATE / type: ligand / ID: 5 / Number of copies: 2 / Formula: PLP |
---|---|
Molecular weight | Theoretical: 247.142 Da |
Chemical component information | ![]() ChemComp-PLP: |
-Macromolecule #6: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(tri...
Macromolecule | Name: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate type: ligand / ID: 6 / Number of copies: 13 / Formula: POV |
---|---|
Molecular weight | Theoretical: 760.076 Da |
Chemical component information | ![]() ChemComp-POV: |
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
![]() | single particle reconstruction |
Aggregation state | particle |
-
Sample preparation
Buffer | pH: 8 |
---|---|
Vitrification | Cryogen name: ETHANE |
-
Electron microscopy
Microscope | FEI TALOS ARCTICA |
---|---|
Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 72.53 e/Å2 |
Electron beam | Acceleration voltage: 200 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | ![]() Model: Talos Arctica / Image courtesy: FEI Company |
-
Image processing
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.1 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 198543 |
---|---|
Initial angle assignment | Type: ANGULAR RECONSTITUTION |
Final angle assignment | Type: ANGULAR RECONSTITUTION |