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- EMDB-20238: Dimeric structure of ACAT1 -

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Basic information

Entry
Database: EMDB / ID: EMD-20238
TitleDimeric structure of ACAT1
Map dataDimeric structure of ACAT1
Sample
  • Complex: ACAT1
    • Protein or peptide: Sterol O-acyltransferase 1
  • Ligand: S-{(3R,5R,9R)-1-[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-4-hydroxy-3-(phosphonooxy)tetrahydrofuran-2-yl]-3,5,9-trihydroxy-8,8-dimethyl-3,5-dioxido-10,14-dioxo-2,4,6-trioxa-11,15-diaza-3lambda~5~,5lambda~5~-diphosphaheptadecan-17-yl} (9Z)-octadec-9-enethioate (non-preferred name)
KeywordsMBOAT / TRANSFERASE
Function / homology
Function and homology information


sterol O-acyltransferase / sterol O-acyltransferase activity / cholesterol O-acyltransferase activity / cholesterol storage / positive regulation of amyloid precursor protein biosynthetic process / very-low-density lipoprotein particle assembly / low-density lipoprotein particle clearance / fatty-acyl-CoA binding / LDL clearance / cholesterol efflux ...sterol O-acyltransferase / sterol O-acyltransferase activity / cholesterol O-acyltransferase activity / cholesterol storage / positive regulation of amyloid precursor protein biosynthetic process / very-low-density lipoprotein particle assembly / low-density lipoprotein particle clearance / fatty-acyl-CoA binding / LDL clearance / cholesterol efflux / cholesterol binding / macrophage derived foam cell differentiation / cholesterol metabolic process / cholesterol homeostasis / endoplasmic reticulum membrane / endoplasmic reticulum / membrane / identical protein binding
Similarity search - Function
Sterol O-acyltransferase, metazoa / Sterol O-acyltransferase, ACAT/DAG/ARE types / Membrane bound O-acyl transferase, MBOAT / MBOAT, membrane-bound O-acyltransferase family
Similarity search - Domain/homology
Sterol O-acyltransferase 1
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.0 Å
AuthorsYan N / Qian HW
Funding support United States, 1 items
OrganizationGrant numberCountry
National Science Foundation (NSF, United States)DMR-1420541 United States
CitationJournal: Nature / Year: 2020
Title: Structural basis for catalysis and substrate specificity of human ACAT1.
Authors: Hongwu Qian / Xin Zhao / Renhong Yan / Xia Yao / Shuai Gao / Xue Sun / Ximing Du / Hongyuan Yang / Catherine C L Wong / Nieng Yan /
Abstract: As members of the membrane-bound O-acyltransferase (MBOAT) enzyme family, acyl-coenzyme A:cholesterol acyltransferases (ACATs) catalyse the transfer of an acyl group from acyl-coenzyme A to ...As members of the membrane-bound O-acyltransferase (MBOAT) enzyme family, acyl-coenzyme A:cholesterol acyltransferases (ACATs) catalyse the transfer of an acyl group from acyl-coenzyme A to cholesterol to generate cholesteryl ester, the primary form in which cholesterol is stored in cells and transported in plasma. ACATs have gained attention as potential drug targets for the treatment of diseases such as atherosclerosis, Alzheimer's disease and cancer. Here we present the cryo-electron microscopy structure of human ACAT1 as a dimer of dimers. Each protomer consists of nine transmembrane segments, which enclose a cytosolic tunnel and a transmembrane tunnel that converge at the predicted catalytic site. Evidence from structure-guided mutational analyses suggests that acyl-coenzyme A enters the active site through the cytosolic tunnel, whereas cholesterol may enter from the side through the transmembrane tunnel. This structural and biochemical characterization helps to rationalize the preference of ACAT1 for unsaturated acyl chains, and provides insight into the catalytic mechanism of enzymes within the MBOAT family.
History
DepositionMay 21, 2019-
Header (metadata) releaseMay 29, 2019-
Map releaseMay 20, 2020-
UpdateMar 20, 2024-
Current statusMar 20, 2024Processing site: RCSB / Status: Released

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Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 0.03
  • Imaged by UCSF Chimera
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  • Surface view colored by cylindrical radius
  • Surface level: 0.03
  • Imaged by UCSF Chimera
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  • Surface view with fitted model
  • Atomic models: PDB-6p2j
  • Surface level: 0.03
  • Imaged by UCSF Chimera
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Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

emd_20238.png

Downloads & links

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Map

FileDownload / File: emd_20238.map.gz / Format: CCP4 / Size: 83.7 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationDimeric structure of ACAT1
Voxel sizeX=Y=Z: 1.114 Å
Density
Contour LevelBy EMDB: 0.03 / Movie #1: 0.03
Minimum - Maximum-0.10035255 - 0.15869217
Average (Standard dev.)-0.00006948075 (±0.0031424758)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions280280280
Spacing280280280
CellA=B=C: 311.91998 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z1.1141.1141.114
M x/y/z280280280
origin x/y/z0.0000.0000.000
length x/y/z311.920311.920311.920
α/β/γ90.00090.00090.000
MAP C/R/S123
start NC/NR/NS000
NC/NR/NS280280280
D min/max/mean-0.1000.159-0.000

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Supplemental data

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Sample components

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Entire : ACAT1

EntireName: ACAT1
Components
  • Complex: ACAT1
    • Protein or peptide: Sterol O-acyltransferase 1
  • Ligand: S-{(3R,5R,9R)-1-[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-4-hydroxy-3-(phosphonooxy)tetrahydrofuran-2-yl]-3,5,9-trihydroxy-8,8-dimethyl-3,5-dioxido-10,14-dioxo-2,4,6-trioxa-11,15-diaza-3lambda~5~,5lambda~5~-diphosphaheptadecan-17-yl} (9Z)-octadec-9-enethioate (non-preferred name)

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Supramolecule #1: ACAT1

SupramoleculeName: ACAT1 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: Sterol O-acyltransferase 1

MacromoleculeName: Sterol O-acyltransferase 1 / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO / EC number: sterol O-acyltransferase
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 69.745375 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MADYKDDDDK SGPDEVDASG RMVGEEKMSL RNRLSKSREN PEEDEDQRNP AKESLETPSN GRIDIKQLIA KKIKLTAEAE ELKPFFMKE VGSHFDDFVT NLIEKSASLD NGGCALTTFS VLEGEKNNHR AKDLRAPPEQ GKIFIARRSL LDELLEVDHI R TIYHMFIA ...String:
MADYKDDDDK SGPDEVDASG RMVGEEKMSL RNRLSKSREN PEEDEDQRNP AKESLETPSN GRIDIKQLIA KKIKLTAEAE ELKPFFMKE VGSHFDDFVT NLIEKSASLD NGGCALTTFS VLEGEKNNHR AKDLRAPPEQ GKIFIARRSL LDELLEVDHI R TIYHMFIA LLILFILSTL VVDYIDEGRL VLEFSLLSYA FGKFPTVVWT WWIMFLSTFS VPYFLFQHWA TGYSKSSHPL IR SLFHGFL FMIFQIGVLG FGPTYVVLAY TLPPASRFII IFEQIRFVMK AHSFVRENVP RVLNSAKEKS STVPIPTVNQ YLY FLFAPT LIYRDSYPRN PTVRWGYVAM KFAQVFGCFF YVYYIFERLC APLFRNIKQE PFSARVLVLC VFNSILPGVL ILFL TFFAF LHCWLNAFAE MLRFGDRMFY KDWWNSTSYS NYYRTWNVVV HDWLYYYAYK DFLWFFSKRF KSAAMLAVFA VSAVV HEYA LAVCLSFFYP VLFVLFMFFG MAFNFIVNDS RKKPIWNVLM WTSLFLGNGV LLCFYSQEWY ARQHCPLKNP TFLDYV RPR SWTCRYVFLE GSDEVDAVEG SHHHHHHHHH H

UniProtKB: Sterol O-acyltransferase 1

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Macromolecule #2: S-{(3R,5R,9R)-1-[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-4-hydrox...

MacromoleculeName: S-{(3R,5R,9R)-1-[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-4-hydroxy-3-(phosphonooxy)tetrahydrofuran-2-yl]-3,5,9-trihydroxy-8,8-dimethyl-3,5-dioxido-10,14-dioxo-2,4,6-trioxa-11,15-diaza- ...Name: S-{(3R,5R,9R)-1-[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-4-hydroxy-3-(phosphonooxy)tetrahydrofuran-2-yl]-3,5,9-trihydroxy-8,8-dimethyl-3,5-dioxido-10,14-dioxo-2,4,6-trioxa-11,15-diaza-3lambda~5~,5lambda~5~-diphosphaheptadecan-17-yl} (9Z)-octadec-9-enethioate (non-preferred name)
type: ligand / ID: 2 / Number of copies: 2 / Formula: 3VV
Molecular weightTheoretical: 1.03198 KDa
Chemical component information

ChemComp-3VV:
S-{(3R,5R,9R)-1-[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-4-hydroxy-3-(phosphonooxy)tetrahydrofuran-2-yl]-3,5,9-trihydroxy-8,8-dimethyl-3,5-dioxido-10,14-dioxo-2,4,6-trioxa-11,15-diaza-3lambda~5~,5lambda~5~-diphosphaheptadecan-17-yl} (9Z)-octadec-9-enethioate (non-preferred name)

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 8
GridDetails: unspecified
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy
Image recordingFilm or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 50.0 e/Å2
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Startup modelType of model: OTHER
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.0 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 358264

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