+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-28552 | |||||||||
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Title | Human Membrane-bound O-acyltransferase 7 | |||||||||
Map data | ||||||||||
Sample |
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Keywords | lipid metabolism membrane remodeling / MEMBRANE PROTEIN | |||||||||
Function / homology | Function and homology information 2-acylglycerol-3-phosphate O-acyltransferase activity / 1-acylglycerol-3-phosphate O-acyltransferase activity / phosphatidylinositol acyl-chain remodeling / lysophospholipid acyltransferase activity / regulation of triglyceride metabolic process / lipid modification / phosphatidylcholine acyl-chain remodeling / O-acyltransferase activity / Acyl chain remodelling of PI / mitochondria-associated endoplasmic reticulum membrane contact site ...2-acylglycerol-3-phosphate O-acyltransferase activity / 1-acylglycerol-3-phosphate O-acyltransferase activity / phosphatidylinositol acyl-chain remodeling / lysophospholipid acyltransferase activity / regulation of triglyceride metabolic process / lipid modification / phosphatidylcholine acyl-chain remodeling / O-acyltransferase activity / Acyl chain remodelling of PI / mitochondria-associated endoplasmic reticulum membrane contact site / layer formation in cerebral cortex / ventricular system development / phosphatidylinositol biosynthetic process / Transferases; Acyltransferases; Transferring groups other than aminoacyl groups / endoplasmic reticulum membrane / endoplasmic reticulum / membrane Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.7 Å | |||||||||
Authors | Wang K / Liao M / Farese RV / Walther TC | |||||||||
Funding support | United States, 2 items
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Citation | Journal: Nat Commun / Year: 2023 Title: The structure of phosphatidylinositol remodeling MBOAT7 reveals its catalytic mechanism and enables inhibitor identification. Authors: Kun Wang / Chia-Wei Lee / Xuewu Sui / Siyoung Kim / Shuhui Wang / Aidan B Higgs / Aaron J Baublis / Gregory A Voth / Maofu Liao / Tobias C Walther / Robert V Farese / Abstract: Cells remodel glycerophospholipid acyl chains via the Lands cycle to adjust membrane properties. Membrane-bound O-acyltransferase (MBOAT) 7 acylates lyso-phosphatidylinositol (lyso-PI) with ...Cells remodel glycerophospholipid acyl chains via the Lands cycle to adjust membrane properties. Membrane-bound O-acyltransferase (MBOAT) 7 acylates lyso-phosphatidylinositol (lyso-PI) with arachidonyl-CoA. MBOAT7 mutations cause brain developmental disorders, and reduced expression is linked to fatty liver disease. In contrast, increased MBOAT7 expression is linked to hepatocellular and renal cancers. The mechanistic basis of MBOAT7 catalysis and substrate selectivity are unknown. Here, we report the structure and a model for the catalytic mechanism of human MBOAT7. Arachidonyl-CoA and lyso-PI access the catalytic center through a twisted tunnel from the cytosol and lumenal sides, respectively. N-terminal residues on the ER lumenal side determine phospholipid headgroup selectivity: swapping them between MBOATs 1, 5, and 7 converts enzyme specificity for different lyso-phospholipids. Finally, the MBOAT7 structure and virtual screening enabled identification of small-molecule inhibitors that may serve as lead compounds for pharmacologic development. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_28552.map.gz | 49.3 MB | EMDB map data format | |
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Header (meta data) | emd-28552-v30.xml emd-28552.xml | 14.3 KB 14.3 KB | Display Display | EMDB header |
Images | emd_28552.png | 115.1 KB | ||
Others | emd_28552_half_map_1.map.gz emd_28552_half_map_2.map.gz | 49.5 MB 49.5 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-28552 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-28552 | HTTPS FTP |
-Related structure data
Related structure data | 8ercMC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_28552.map.gz / Format: CCP4 / Size: 52.7 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 0.825 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_28552_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_28552_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Membrane-bound O-acyltransferase 7
Entire | Name: Membrane-bound O-acyltransferase 7 |
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Components |
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-Supramolecule #1: Membrane-bound O-acyltransferase 7
Supramolecule | Name: Membrane-bound O-acyltransferase 7 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all / Details: Purified protein |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 55 kDa/nm |
-Macromolecule #1: Lysophospholipid acyltransferase 7
Macromolecule | Name: Lysophospholipid acyltransferase 7 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO EC number: Transferases; Acyltransferases; Transferring groups other than aminoacyl groups |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 54.196277 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MSPEEWTYLV VLLISIPIGF LFKKAGPGLK RWGAAAVGLG LTLFTCGPHT LHSLVTILGT WALIQAQPCS CHALALAWTF SYLLFFRAL SLLGLPTPTP FTNAVQLLLT LKLVSLASEV QDLHLAQRKE MASGFSKGPT LGLLPDVPSL METLSYSYCY V GIMTGPFF ...String: MSPEEWTYLV VLLISIPIGF LFKKAGPGLK RWGAAAVGLG LTLFTCGPHT LHSLVTILGT WALIQAQPCS CHALALAWTF SYLLFFRAL SLLGLPTPTP FTNAVQLLLT LKLVSLASEV QDLHLAQRKE MASGFSKGPT LGLLPDVPSL METLSYSYCY V GIMTGPFF RYRTYLDWLE QPFPGAVPSL RPLLRRAWPA PLFGLLFLLS SHLFPLEAVR EDAFYARPLP ARLFYMIPVF FA FRMRFYV AWIAAECGCI AAGFGAYPVA AKARAGGGPT LQCPPPSSPE KAASLEYDYE TIRNIDCYST DFCVRVRDGM RYW NMTVQW WLAQYIYKSA PARSYVLRSA WTMLLSAYWH GLHPGYYLSF LTIPLCLAAE GRLESALRGR LSPGGQKAWD WVHW FLKMR AYDYMCMGFV LLSLADTLRY WASIYFCIHF LALAALGLGL ALGGGSPSRR KAASQPTSLA PEKLREELEA CGIEN LYFQ UniProtKB: Lysophospholipid acyltransferase 7 |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | 2D array |
-Sample preparation
Concentration | 6 mg/mL |
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Buffer | pH: 7.5 |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: OTHER / Nominal defocus max: 2.2 µm / Nominal defocus min: 0.8 µm |
Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 55.5 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: OTHER Details: Initial model were generated using ab initio construction in cryoSPARC |
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Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.7 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 206418 |