[English] 日本語
Yorodumi
- PDB-8djm: HMGCR-UBIAD1 Complex State 1 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8djm
TitleHMGCR-UBIAD1 Complex State 1
Components
  • 3-hydroxy-3-methylglutaryl-coenzyme A reductase
  • Fab 15B2 Heavy Chain
  • Fab 15B2 Light Chain
  • Soluble cytochrome b562
  • UbiA prenyltransferase domain-containing protein 1
KeywordsOxidoreductase/Immune System / Cholesterol / MEMBRANE PROTEIN / Oxidoreductase-Immune System complex
Function / homology
Function and homology information


4-hydroxybenzoate polyprenyltransferase / vitamin K biosynthetic process / : / hydroxymethylglutaryl-CoA reductase (NADPH) / hydroxymethylglutaryl-CoA reductase (NADPH) activity / GTPase regulator activity / coenzyme A binding / negative regulation of amyloid-beta clearance / prenyltransferase activity / menaquinone biosynthetic process ...4-hydroxybenzoate polyprenyltransferase / vitamin K biosynthetic process / : / hydroxymethylglutaryl-CoA reductase (NADPH) / hydroxymethylglutaryl-CoA reductase (NADPH) activity / GTPase regulator activity / coenzyme A binding / negative regulation of amyloid-beta clearance / prenyltransferase activity / menaquinone biosynthetic process / coenzyme A metabolic process / ubiquinone biosynthetic process / isoprenoid biosynthetic process / peroxisomal membrane / cholesterol biosynthetic process / antioxidant activity / negative regulation of protein secretion / regulation of ERK1 and ERK2 cascade / NADPH binding / electron transport chain / negative regulation of protein catabolic process / visual learning / long-term synaptic potentiation / periplasmic space / electron transfer activity / iron ion binding / Golgi membrane / heme binding / endoplasmic reticulum membrane / endoplasmic reticulum / nucleus
Similarity search - Function
UbiA prenyltransferase domain containing protein 1 / UbiA prenyltransferase family / UbiA prenyltransferase superfamily / UbiA prenyltransferase family / Hydroxymethylglutaryl-CoA reductase, metazoan / Hydroxymethylglutaryl-CoA reductase, eukaryotic/archaeal type / Hydroxymethylglutaryl-CoA reductase, N-terminal / Hydroxymethylglutaryl-coenzyme A reductases signature 2. / Hydroxymethylglutaryl-coenzyme A reductases signature 1. / Hydroxymethylglutaryl-coenzyme A reductases signature 3. ...UbiA prenyltransferase domain containing protein 1 / UbiA prenyltransferase family / UbiA prenyltransferase superfamily / UbiA prenyltransferase family / Hydroxymethylglutaryl-CoA reductase, metazoan / Hydroxymethylglutaryl-CoA reductase, eukaryotic/archaeal type / Hydroxymethylglutaryl-CoA reductase, N-terminal / Hydroxymethylglutaryl-coenzyme A reductases signature 2. / Hydroxymethylglutaryl-coenzyme A reductases signature 1. / Hydroxymethylglutaryl-coenzyme A reductases signature 3. / Hydroxymethylglutaryl-CoA reductase, class I/II / Hydroxymethylglutaryl-CoA reductase, class I/II, NAD/NADP-binding domain superfamily / Hydroxymethylglutaryl-CoA reductase, class I/II, substrate-binding domain superfamily / Hydroxymethylglutaryl-CoA reductase, class I/II, catalytic domain superfamily / Hydroxymethylglutaryl-CoA reductase, class I/II, conserved site / Hydroxymethylglutaryl-coenzyme A reductase / Hydroxymethylglutaryl-coenzyme A reductases family profile. / : / Sterol-sensing domain of SREBP cleavage-activation / Sterol-sensing domain (SSD) profile. / Sterol-sensing domain / Cytochrome b562 / Cytochrome b562 / Cytochrome c/b562 / Immunoglobulins / Immunoglobulin-like / Sandwich / Mainly Beta
Similarity search - Domain/homology
CHOLESTEROL HEMISUCCINATE / UbiA prenyltransferase domain-containing protein 1 / 3-hydroxy-3-methylglutaryl-coenzyme A reductase / Soluble cytochrome b562
Similarity search - Component
Biological speciesCricetulus griseus (Chinese hamster)
Escherichia coli (E. coli)
Mus musculus (house mouse)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.23 Å
AuthorsChen, H. / Qi, X. / Li, X.
Funding support United States, 2items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS) United States
Welch Foundation United States
CitationJournal: Nat Commun / Year: 2022
Title: Regulated degradation of HMG CoA reductase requires conformational changes in sterol-sensing domain.
Authors: Hongwen Chen / Xiaofeng Qi / Rebecca A Faulkner / Marc M Schumacher / Linda M Donnelly / Russell A DeBose-Boyd / Xiaochun Li /
Abstract: 3-Hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) is the rate-limiting enzyme in cholesterol synthesis and target of cholesterol-lowering statin drugs. Accumulation of sterols in endoplasmic ...3-Hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) is the rate-limiting enzyme in cholesterol synthesis and target of cholesterol-lowering statin drugs. Accumulation of sterols in endoplasmic reticulum (ER) membranes accelerates degradation of HMGCR, slowing the synthesis of cholesterol. Degradation of HMGCR is inhibited by its binding to UBIAD1 (UbiA prenyltransferase domain-containing protein-1). This inhibition contributes to statin-induced accumulation of HMGCR, which limits their cholesterol-lowering effects. Here, we report cryo-electron microscopy structures of the HMGCR-UBIAD1 complex, which is maintained by interactions between transmembrane helix (TM) 7 of HMGCR and TMs 2-4 of UBIAD1. Disrupting this interface by mutagenesis prevents complex formation, enhancing HMGCR degradation. TMs 2-6 of HMGCR contain a 170-amino acid sterol sensing domain (SSD), which exists in two conformations-one of which is essential for degradation. Thus, our data supports a model that rearrangement of the TMs in the SSD permits recruitment of proteins that initate HMGCR degradation, a key reaction in the regulatory system that governs cholesterol synthesis.
History
DepositionJul 1, 2022Deposition site: RCSB / Processing site: RCSB
Revision 1.0Aug 3, 2022Provider: repository / Type: Initial release
Revision 1.1Nov 6, 2024Group: Data collection / Structure summary
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / em_admin / pdbx_entry_details / pdbx_modification_feature
Item: _em_admin.last_update / _pdbx_entry_details.has_protein_modification

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: 3-hydroxy-3-methylglutaryl-coenzyme A reductase
B: UbiA prenyltransferase domain-containing protein 1
C: Soluble cytochrome b562
L: Fab 15B2 Light Chain
H: Fab 15B2 Heavy Chain
hetero molecules


Theoretical massNumber of molelcules
Total (without water)141,39513
Polymers136,0165
Non-polymers5,3798
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_5551

-
Components

-
Protein , 3 types, 3 molecules ABC

#1: Protein 3-hydroxy-3-methylglutaryl-coenzyme A reductase / HMG-CoA reductase


Mass: 41215.859 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Cricetulus griseus (Chinese hamster) / Gene: HMGCR / Production host: Homo sapiens (human)
References: UniProt: P00347, hydroxymethylglutaryl-CoA reductase (NADPH)
#2: Protein UbiA prenyltransferase domain-containing protein 1


Mass: 32780.508 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Cricetulus griseus (Chinese hamster) / Gene: Ubiad1, CgPICR_017873, H671_2g6271, I79_022097 / Production host: Homo sapiens (human) / References: UniProt: G3IEF0
#3: Protein Soluble cytochrome b562 / Cytochrome b-562


Mass: 13470.236 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Escherichia coli (E. coli) / Gene: cybC / Production host: Homo sapiens (human) / References: UniProt: P0ABE7

-
Antibody , 2 types, 2 molecules LH

#4: Antibody Fab 15B2 Light Chain


Mass: 23373.771 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus (house mouse) / Production host: Homo sapiens (human)
#5: Antibody Fab 15B2 Heavy Chain


Mass: 25175.154 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus (house mouse) / Production host: Homo sapiens (human)

-
Non-polymers , 2 types, 8 molecules

#6: Chemical
ChemComp-Y01 / CHOLESTEROL HEMISUCCINATE


Mass: 486.726 Da / Num. of mol.: 6 / Source method: obtained synthetically / Formula: C31H50O4
#7: Chemical ChemComp-AJP / Digitonin


Mass: 1229.312 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C56H92O29 / Comment: detergent*YM

-
Details

Has ligand of interestN
Has protein modificationY

-
Experimental details

-
Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

-
Sample preparation

Component
IDNameTypeEntity IDParent-IDSource
1HMGCR-UBIAD1-BRIL-Fab 15B2 complexCOMPLEX#1-#50RECOMBINANT
2HMGCR-UBIAD1-BRIL-Fab 15B2 complexCOMPLEX#1-#51RECOMBINANT
Source (natural)Organism: Cricetulus griseus (Chinese hamster)
Source (recombinant)Organism: Homo sapiens (human)
Buffer solutionpH: 7.5
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

-
Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 2000 nm / Nominal defocus min: 1000 nm
Image recordingElectron dose: 8.5 e/Å2 / Film or detector model: GATAN K3 (6k x 4k)

-
Processing

SoftwareName: REFMAC / Version: 5.8.0158 / Classification: refinement
CTF correctionType: NONE
3D reconstructionResolution: 3.23 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 215396 / Symmetry type: POINT
RefinementResolution: 3.23→269.44 Å / Cor.coef. Fo:Fc: 0.799 / SU B: 14.987 / SU ML: 0.22 / ESU R: 0.116 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflection
Rwork0.46709 --
obs0.46709 1215898 100 %
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso mean: 139.858 Å2
Baniso -1Baniso -2Baniso -3
1--1.97 Å21.57 Å2-2.05 Å2
2--1.03 Å21.32 Å2
3---0.94 Å2
Refinement stepCycle: 1 / Total: 7032
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
ELECTRON MICROSCOPYr_bond_refined_d0.0090.0197207
ELECTRON MICROSCOPYr_bond_other_d0.0060.026889
ELECTRON MICROSCOPYr_angle_refined_deg1.3782.0239833
ELECTRON MICROSCOPYr_angle_other_deg0.993315973
ELECTRON MICROSCOPYr_dihedral_angle_1_deg6.2425851
ELECTRON MICROSCOPYr_dihedral_angle_2_deg33.21623.225276
ELECTRON MICROSCOPYr_dihedral_angle_3_deg13.947151148
ELECTRON MICROSCOPYr_dihedral_angle_4_deg14.4211540
ELECTRON MICROSCOPYr_chiral_restr0.0830.21175
ELECTRON MICROSCOPYr_gen_planes_refined0.0050.027559
ELECTRON MICROSCOPYr_gen_planes_other0.0010.021449
ELECTRON MICROSCOPYr_nbd_refined
ELECTRON MICROSCOPYr_nbd_other
ELECTRON MICROSCOPYr_nbtor_refined
ELECTRON MICROSCOPYr_nbtor_other
ELECTRON MICROSCOPYr_xyhbond_nbd_refined
ELECTRON MICROSCOPYr_xyhbond_nbd_other
ELECTRON MICROSCOPYr_metal_ion_refined
ELECTRON MICROSCOPYr_metal_ion_other
ELECTRON MICROSCOPYr_symmetry_vdw_refined
ELECTRON MICROSCOPYr_symmetry_vdw_other
ELECTRON MICROSCOPYr_symmetry_hbond_refined
ELECTRON MICROSCOPYr_symmetry_hbond_other
ELECTRON MICROSCOPYr_symmetry_metal_ion_refined
ELECTRON MICROSCOPYr_symmetry_metal_ion_other
ELECTRON MICROSCOPYr_mcbond_it2.18514.4643437
ELECTRON MICROSCOPYr_mcbond_other2.18614.4663436
ELECTRON MICROSCOPYr_mcangle_it4.18921.6744277
ELECTRON MICROSCOPYr_mcangle_other4.18921.6724278
ELECTRON MICROSCOPYr_scbond_it1.16114.1943770
ELECTRON MICROSCOPYr_scbond_other1.16114.1943769
ELECTRON MICROSCOPYr_scangle_it
ELECTRON MICROSCOPYr_scangle_other2.44221.1295557
ELECTRON MICROSCOPYr_long_range_B_refined10.2538214
ELECTRON MICROSCOPYr_long_range_B_other10.2528215
ELECTRON MICROSCOPYr_rigid_bond_restr
ELECTRON MICROSCOPYr_sphericity_free
ELECTRON MICROSCOPYr_sphericity_bonded
LS refinement shellResolution: 3.23→3.314 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rwork3.004 90513 -
Rfree-0 -
obs--100 %

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more