[English] 日本語
Yorodumi
- EMDB-44917: Structure of GGCX-BGP complex -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-44917
TitleStructure of GGCX-BGP complex
Map data
Sample
  • Complex: GGCX-BGP complex
    • Protein or peptide: Vitamin K-dependent gamma-carboxylase
    • Protein or peptide: Osteocalcin
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
  • Ligand: CHOLESTEROL
  • Ligand: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate
Keywordsvitamin K cycle / MEMBRANE PROTEIN / LYASE-SUBSTRATE complex
Function / homology
Function and homology information


structural constituent of bone / hydroxyapatite binding / peptidyl-glutamate 4-carboxylase / gamma-glutamyl carboxylase activity / negative regulation of bone development / response to macrophage colony-stimulating factor / Defective gamma-carboxylation of F9 / vitamin binding / vitamin K metabolic process / regulation of testosterone biosynthetic process ...structural constituent of bone / hydroxyapatite binding / peptidyl-glutamate 4-carboxylase / gamma-glutamyl carboxylase activity / negative regulation of bone development / response to macrophage colony-stimulating factor / Defective gamma-carboxylation of F9 / vitamin binding / vitamin K metabolic process / regulation of testosterone biosynthetic process / response to gravity / response to vitamin K / regulation of osteoclast differentiation / cellular response to zinc ion starvation / type B pancreatic cell proliferation / cellular response to vitamin D / regulation of bone mineralization / response to vitamin D / regulation of bone resorption / osteoblast development / response to hydroxyisoflavone / positive regulation of neurotransmitter secretion / response to zinc ion / bone mineralization / RUNX2 regulates osteoblast differentiation / response to testosterone / Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus / Gamma-carboxylation of protein precursors / Removal of aminoterminal propeptides from gamma-carboxylated proteins / response to glucocorticoid / response to mechanical stimulus / regulation of cellular response to insulin stimulus / protein maturation / response to activity / skeletal system development / stem cell differentiation / brain development / cellular response to growth factor stimulus / protein modification process / hormone activity / bone development / Golgi lumen / cognition / cellular response to insulin stimulus / response to estrogen / osteoblast differentiation / blood coagulation / glucose homeostasis / vesicle / perikaryon / response to ethanol / learning or memory / cell adhesion / endoplasmic reticulum lumen / response to xenobiotic stimulus / dendrite / calcium ion binding / endoplasmic reticulum membrane / structural molecule activity / extracellular space / extracellular region / membrane / cytoplasm
Similarity search - Function
Osteocalcin/matrix Gla protein / Osteocalcin / Vitamin K-dependent gamma-carboxylase / HTTM / : / : / HTTM domain / Vitamin K-dependent gamma-carboxylase, lumenal domain / Horizontally Transferred TransMembrane Domain / RmlC-like cupin domain superfamily ...Osteocalcin/matrix Gla protein / Osteocalcin / Vitamin K-dependent gamma-carboxylase / HTTM / : / : / HTTM domain / Vitamin K-dependent gamma-carboxylase, lumenal domain / Horizontally Transferred TransMembrane Domain / RmlC-like cupin domain superfamily / Gamma-carboxyglutamic acid-rich (GLA) domain / Gamma-carboxyglutamic acid-rich (GLA) domain superfamily / Vitamin K-dependent carboxylation domain. / Gla domain profile. / Domain containing Gla (gamma-carboxyglutamate) residues. / RmlC-like jelly roll fold
Similarity search - Domain/homology
Osteocalcin / Vitamin K-dependent gamma-carboxylase
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.95 Å
AuthorsWang R / Qi X
Funding support United States, 1 items
OrganizationGrant numberCountry
Cancer Prevention and Research Institute of Texas (CPRIT)RR230054 United States
CitationJournal: Nature / Year: 2025
Title: Structure and mechanism of vitamin-K-dependent γ-glutamyl carboxylase.
Authors: Rong Wang / Baozhi Chen / Nadia Elghobashi-Meinhardt / Jian-Ke Tie / Alyssa Ayala / Ning Zhou / Xiaofeng Qi /
Abstract: γ-Glutamyl carboxylase (GGCX) is the sole identified enzyme that uses vitamin K (VK) as a cofactor in humans. This protein catalyses the oxidation of VK hydroquinone to convert specific glutamate ...γ-Glutamyl carboxylase (GGCX) is the sole identified enzyme that uses vitamin K (VK) as a cofactor in humans. This protein catalyses the oxidation of VK hydroquinone to convert specific glutamate residues to γ-carboxyglutamate residues in VK-dependent proteins (VDPs), which are involved in various essential biological processes and diseases. However, the working mechanism of GGCX remains unclear. Here we report three cryogenic electron microscopy structures of human GGCX: in the apo state, bound to osteocalcin (a VDP) and bound to VK. The propeptide of the VDP binds to the lumenal domain of GGCX, which stabilizes transmembrane helices 6 and 7 of GGCX to create the VK-binding pocket. After binding of VK, residue Lys218 in GGCX mediates the oxidation of VK hydroxyquinone, which leads to the deprotonation of glutamate residues and the construction of γ-carboxyglutamate residues. Our structural observations and results from binding and cell biological assays and molecular dynamics simulations show that a cholesterol molecule interacts with the transmembrane helices of GGCX to regulate its protein levels in cells. Together, these results establish a link between cholesterol metabolism and VK-dependent pathways.
History
DepositionMay 17, 2024-
Header (metadata) releaseJan 29, 2025-
Map releaseJan 29, 2025-
UpdateMar 26, 2025-
Current statusMar 26, 2025Processing site: RCSB / Status: Released

-
Structure visualization

Supplemental images

emd_44917.png

Downloads & links

-
Map

FileDownload / File: emd_44917.map.gz / Format: CCP4 / Size: 83.7 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.83 Å/pix.
x 280 pix.
= 232.4 Å		0.83 Å/pix.
x 280 pix.
= 232.4 Å		0.83 Å/pix.
x 280 pix.
= 232.4 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.83 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.367
Minimum - Maximum-3.332911 - 4.3434587
Average (Standard dev.)0.000011056648 (±0.08732307)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions280280280
Spacing280280280
CellA=B=C: 232.4 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Half map: #2

Fileemd_44917_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #1

Fileemd_44917_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : GGCX-BGP complex

EntireName: GGCX-BGP complex
Components
  • Complex: GGCX-BGP complex
    • Protein or peptide: Vitamin K-dependent gamma-carboxylase
    • Protein or peptide: Osteocalcin
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
  • Ligand: CHOLESTEROL
  • Ligand: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate

-
Supramolecule #1: GGCX-BGP complex

SupramoleculeName: GGCX-BGP complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2
Source (natural)Organism: Homo sapiens (human)

-
Macromolecule #1: Vitamin K-dependent gamma-carboxylase

MacromoleculeName: Vitamin K-dependent gamma-carboxylase / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO / EC number: peptidyl-glutamate 4-carboxylase
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 88.652609 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MAVSAGSART SPSSDKVQKD KAELISGPRQ DSRIGKLLGF EWTDLSSWRR LVTLLNRPTD PASLAVFRFL FGFLMVLDIP QERGLSSLD RKYLDGLDVC RFPLLDALRP LPLDWMYLVY TIMFLGALGM MLGLCYRISC VLFLLPYWYV FLLDKTSWNN H SYLYGLLA ...String:
MAVSAGSART SPSSDKVQKD KAELISGPRQ DSRIGKLLGF EWTDLSSWRR LVTLLNRPTD PASLAVFRFL FGFLMVLDIP QERGLSSLD RKYLDGLDVC RFPLLDALRP LPLDWMYLVY TIMFLGALGM MLGLCYRISC VLFLLPYWYV FLLDKTSWNN H SYLYGLLA FQLTFMDANH YWSVDGLLNA HRRNAHVPLW NYAVLRGQIF IVYFIAGVKK LDADWVEGYS MEYLSRHWLF SP FKLLLSE ELTSLLVVHW GGLLLDLSAG FLLFFDVSRS IGLFFVSYFH CMNSQLFSIG MFSYVMLASS PLFCSPEWPR KLV SYCPRR LQQLLPLKAA PQPSVSCVYK RSRGKSGQKP GLRHQLGAAF TLLYLLEQLF LPYSHFLTQG YNNWTNGLYG YSWD MMVHS RSHQHVKITY RDGRTGELGY LNPGVFTQSR RWKDHADMLK QYATCLSRLL PKYNVTEPQI YFDIWVSIND RFQQR IFDP RVDIVQAAWS PFQRTSWVQP LLMDLSPWRA KLQEIKSSLD NHTEVVFIAD FPGLHLENFV SEDLGNTSIQ LLQGEV TVE LVAEQKNQTL REGEKMQLPA GEYHKVYTTS PSPSCYMYVY VNTTELALEQ DLAYLQELKE KVENGSETGP LPPELQP LL EGEVKGGPEP TPLVQTFLRR QQRLQEIERR RNTPFHERFF RFLLRKLYVF RRSFLMTCIS LRNLILGRPS LEQLAQEV T YANLRPFEAV GELNPSNTDS SHSNPPESNP DPVHSEFDYK DDDDK

UniProtKB: Vitamin K-dependent gamma-carboxylase

-
Macromolecule #2: Osteocalcin

MacromoleculeName: Osteocalcin / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 11.804439 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
MRALTLLALL ALAALCIAGQ AGAKPSGAES SKGAAFVSKQ EGSEVVKRPR RYLYQWLGAP VPYPDPLEPR REVCELNPDC DELADHIGF QEAYRRFYGP VHHHHHH

UniProtKB: Osteocalcin

-
Macromolecule #4: 2-acetamido-2-deoxy-beta-D-glucopyranose

MacromoleculeName: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 4 / Number of copies: 2 / Formula: NAG
Molecular weightTheoretical: 221.208 Da
Chemical component information

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

-
Macromolecule #5: CHOLESTEROL

MacromoleculeName: CHOLESTEROL / type: ligand / ID: 5 / Number of copies: 1 / Formula: CLR
Molecular weightTheoretical: 386.654 Da
Chemical component information

ChemComp-CLR:
CHOLESTEROL

-
Macromolecule #6: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(tri...

MacromoleculeName: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate
type: ligand / ID: 6 / Number of copies: 1 / Formula: POV
Molecular weightTheoretical: 760.076 Da
Chemical component information

ChemComp-POV:
(2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate / phospholipid*YM

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

BufferpH: 7.5
VitrificationCryogen name: ETHANE

-
Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 60.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.0 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

-
Image processing

Startup modelType of model: OTHER
Final reconstructionResolution.type: BY AUTHOR / Resolution: 2.95 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 218162
Initial angle assignmentType: NOT APPLICABLE
Final angle assignmentType: NOT APPLICABLE

+
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