[English] 日本語
Yorodumi
- EMDB-76487: Structural determination of lipid-bound Factor VIII -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-76487
TitleStructural determination of lipid-bound Factor VIII
Map dataDeepEMhancer sharpened map
Sample
  • Complex: Coagulation Factor VIII
    • Protein or peptide: Coagulation factor VIII
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
  • Ligand: CALCIUM ION
  • Ligand: COPPER (II) ION
KeywordsCoagulation / Intrinsic Pathway / Hemophilia / Factor VIII / BLOOD CLOTTING
Function / homology
Function and homology information


Defective F8 accelerates dissociation of the A2 domain / Defective F8 binding to the cell membrane / Defective F8 secretion / Defective F8 sulfation at Y1699 / Gamma carboxylation, hypusinylation, hydroxylation, and arylsulfatase activation / Defective F8 binding to von Willebrand factor / blood coagulation, intrinsic pathway / Cargo concentration in the ER / Defective factor IX causes thrombophilia / Defective cofactor function of FVIIIa variant ...Defective F8 accelerates dissociation of the A2 domain / Defective F8 binding to the cell membrane / Defective F8 secretion / Defective F8 sulfation at Y1699 / Gamma carboxylation, hypusinylation, hydroxylation, and arylsulfatase activation / Defective F8 binding to von Willebrand factor / blood coagulation, intrinsic pathway / Cargo concentration in the ER / Defective factor IX causes thrombophilia / Defective cofactor function of FVIIIa variant / Defective F9 variant does not activate FX / COPII-coated ER to Golgi transport vesicle / COPII-mediated vesicle transport / Defective F8 cleavage by thrombin / : / : / endoplasmic reticulum-Golgi intermediate compartment membrane / platelet alpha granule lumen / acute-phase response / Golgi lumen / blood coagulation / Platelet degranulation / oxidoreductase activity / endoplasmic reticulum lumen / copper ion binding / : / extracellular region / plasma membrane
Similarity search - Function
Coagulation factor 5/8-like / : / Multicopper oxidases, conserved site / Multicopper oxidases signature 1. / Coagulation factors 5/8 type C domain (FA58C) signature 2. / Coagulation factors 5/8 type C domain (FA58C) signature 1. / Coagulation factor 5/8 C-terminal domain, discoidin domain / Coagulation factors 5/8 type C domain (FA58C) profile. / Multicopper oxidase, C-terminal / Multicopper oxidase ...Coagulation factor 5/8-like / : / Multicopper oxidases, conserved site / Multicopper oxidases signature 1. / Coagulation factors 5/8 type C domain (FA58C) signature 2. / Coagulation factors 5/8 type C domain (FA58C) signature 1. / Coagulation factor 5/8 C-terminal domain, discoidin domain / Coagulation factors 5/8 type C domain (FA58C) profile. / Multicopper oxidase, C-terminal / Multicopper oxidase / F5/8 type C domain / Coagulation factor 5/8 C-terminal domain / Multicopper oxidase, N-terminal / Multicopper oxidase / Cupredoxin / Galactose-binding-like domain superfamily
Similarity search - Domain/homology
Coagulation factor VIII
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.46 Å
AuthorsMohammed BM
Funding support United States, 5 items
OrganizationGrant numberCountry
Other privateDoisy Fund of the Edward A. Doisy Department of Biochemistry and Molecular Biology United States
Childrens Discovery Institute of Washington University and St. Louis Childrens HospitalCDI-CORE-2015-505 and CDI-CORE-2019-813 United States
The Foundation for Barnes-Jewish Hospital3770 United States
National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Disease (NIH/NIDDK)DK020579 United States
National Institutes of Health/National Cancer Institute (NIH/NCI)CA091842 United States
CitationJournal: J Thromb Haemost / Year: 2026
Title: Structural determination of lipid-bound Factor VIII.
Authors: Bassem M Mohammed
Abstract: BACKGROUND: Coagulation factor (F)VIII is the inactive precursor of FVIIIa, an essential component of the intrinsic tenase complex. Despite numerous structures of recombinant FVIII in solution, the ...BACKGROUND: Coagulation factor (F)VIII is the inactive precursor of FVIIIa, an essential component of the intrinsic tenase complex. Despite numerous structures of recombinant FVIII in solution, the structural basis of the procofactor-membrane interface remains poorly defined. Traditional liposome platforms require special grids and often suffer from heterogeneous particle distribution and overcrowding, precluding high-resolution single-particle analysis (SPA), while membrane mimetics, nanodiscs, are too planar posing significant biophysical challenges.
OBJECTIVES: To establish a reproducible methodology for structural determination of membrane-bound coagulation factors and resolve the procofactor FVIII-lipid interface.
METHODS: We used methylated branched lipids to compensate for membrane planarity and employed cryo-EM to solve the structure of FVIII bound to lipids.
RESULTS: We resolved the cryo-EM structure of procofactor FVIII on nanodiscs and liposomes lipid membranes at 3.46 - 3.56 Å, respectively. Structural analysis reveals a definitive tilted docking ...RESULTS: We resolved the cryo-EM structure of procofactor FVIII on nanodiscs and liposomes lipid membranes at 3.46 - 3.56 Å, respectively. Structural analysis reveals a definitive tilted docking orientation where both C domains mediate shallow interfacial insertion with the C2 domain acts as the primary anchor and the C1 domain serves as a secondary tether. This spatial arrangement structurally explains the high clinical severity of C2-interface mutations compared to more moderate C1 surface mutations.
CONCLUSION: Methylated branched lipids enable rapid, high-resolution characterization of membrane-associated clotting factors. This structure provides the first definitive template for the FVIII- ...CONCLUSION: Methylated branched lipids enable rapid, high-resolution characterization of membrane-associated clotting factors. This structure provides the first definitive template for the FVIII-lipid interface, serving as a benchmark for future studies on tenase complex assembly.
History
DepositionApr 8, 2026-
Header (metadata) releaseJun 10, 2026-
Map releaseJun 10, 2026-
UpdateJun 10, 2026-
Current statusJun 10, 2026Processing site: RCSB / Status: Released

-
Structure visualization

Supplemental images

emd_76487.png

Downloads & links

-
Map

FileDownload / File: emd_76487.map.gz / Format: CCP4 / Size: 274.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationDeepEMhancer sharpened map
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.93 Å/pix.
x 416 pix.
= 386.048 Å		0.93 Å/pix.
x 416 pix.
= 386.048 Å		0.93 Å/pix.
x 416 pix.
= 386.048 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.928 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.149
Minimum - Maximum-0.0010111738 - 2.6807327
Average (Standard dev.)0.0012722756 (±0.029853348)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions416416416
Spacing416416416
CellA=B=C: 386.04797 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Additional map: Composite map - unsharpened

Fileemd_76487_additional_1.map
AnnotationComposite map - unsharpened
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : Coagulation Factor VIII

EntireName: Coagulation Factor VIII
Components
  • Complex: Coagulation Factor VIII
    • Protein or peptide: Coagulation factor VIII
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
  • Ligand: CALCIUM ION
  • Ligand: COPPER (II) ION

-
Supramolecule #1: Coagulation Factor VIII

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

-
Macromolecule #1: Coagulation factor VIII

MacromoleculeName: Coagulation factor VIII / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 265.061062 KDa
Recombinant expressionOrganism: Mesocricetus auratus (golden hamster)
SequenceString: ATRRYYLGAV ELSWDYMQSD LGELPVDARF PPRVPKSFPF NTSVVYKKTL FVEFTDHLFN IAKPRPPWMG LLGPTIQAEV YDTVVITLK NMASHPVSLH AVGVSYWKAS EGAEYDDQTS QREKEDDKVF PGGSHTYVWQ VLKENGPMAS DPLCLTYSYL S HVDLVKDL ...String:
ATRRYYLGAV ELSWDYMQSD LGELPVDARF PPRVPKSFPF NTSVVYKKTL FVEFTDHLFN IAKPRPPWMG LLGPTIQAEV YDTVVITLK NMASHPVSLH AVGVSYWKAS EGAEYDDQTS QREKEDDKVF PGGSHTYVWQ VLKENGPMAS DPLCLTYSYL S HVDLVKDL NSGLIGALLV CREGSLAKEK TQTLHKFILL FAVFDEGKSW HSETKNSLMQ DRDAASARAW PKMHTVNGYV NR SLPGLIG CHRKSVYWHV IGMGTTPEVH SIFLEGHTFL VRNHRQASLE ISPITFLTAQ TLLMDLGQFL LFCHISSHQH DGM EAYVKV DSCPEEPQLR MKNNEEAEDY DDDLTDSEMD VVRFDDDNSP SFIQIRSVAK KHPKTWVHYI AAEEEDWDYA PLVL APDDR SYKSQYLNNG PQRIGRKYKK VRFMAYTDET FKTREAIQHE SGILGPLLYG EVGDTLLIIF KNQASRPYNI YPHGI TDVR PLYSRRLPKG VKHLKDFPIL PGEIFKYKWT VTVEDGPTKS DPRCLTRYYS SFVNMERDLA SGLIGPLLIC YKESVD QRG NQIMSDKRNV ILFSVFDENR SWYLTENIQR FLPNPAGVQL EDPEFQASNI MHSINGYVFD SLQLSVCLHE VAYWYIL SI GAQTDFLSVF FSGYTFKHKM VYEDTLTLFP FSGETVFMSM ENPGLWILGC HNSDFRNRGM TALLKVSSCD KNTGDYYE D SYEDISAYLL SKNNAIEPRS FSQNSRHPST RQKQFNATTI PENDIEKTDP WFAHRTPMPK IQNVSSSDLL MLLRQSPTP HGLSLSDLQE AKYETFSDDP SPGAIDSNNS LSEMTHFRPQ LHHSGDMVFT PESGLQLRLN EKLGTTAATE LKKLDFKVSS TSNNLISTI PSDNLAAGTD NTSSLGPPSM PVHYDSQLDT TLFGKKSSPL TESGGPLSLS EENNDSKLLE SGLMNSQESS W GKNVSSTE SGRLFKGKRA HGPALLTKDN ALFKVSISLL KTNKTSNNSA TNRKTHIDGP SLLIENSPSV WQNILESDTE FK KVTPLIH DRMLMDKNAT ALRLNHMSNK TTSSKNMEMV QQKKEGPIPP DAQNPDMSFF KMLFLPESAR WIQRTHGKNS LNS GQGPSP KQLVSLGPEK SVEGQNFLSE KNKVVVGKGE FTKDVGLKEM VFPSSRNLFL TNLDNLHENN THNQEKKIQE EIEK KETLI QENVVLPQIH TVTGTKNFMK NLFLLSTRQN VEGSYDGAYA PVLQDFRSLN DSTNRTKKHT AHFSKKGEEE NLEGL GNQT KQIVEKYACT TRISPNTSQQ NFVTQRSKRA LKQFRLPLEE TELEKRIIVD DTSTQWSKNM KHLTPSTLTQ IDYNEK EKG AITQSPLSDC LTRSHSIPQA NRSPLPIAKV SSFPSIRPIY LTRVLFQDNS SHLPAASYRK KDSGVQESSH FLQGAKK NN LSLAILTLEM TGDQREVGSL GTSATNSVTY KKVENTVLPK PDLPKTSGKV ELLPKVHIYQ KDLFPTETSN GSPGHLDL V EGSLLQGTEG AIKWNEANRP GKVPFLRVAT ESSAKTPSKL LDPLAWDNHY GTQIPKEEWK SQEKSPEKTA FKKKDTILS LNACESNHAI AAINEGQNKP EIEVTWAKQG RTERLCSQNP PVLKRHQREI TRTTLQSDQE EIDYDDTISV EMKKEDFDIY DEDENQSPR SFQKKTRHYF IAAVERLWDY GMSSSPHVLR NRAQSGSVPQ FKKVVFQEFT DGSFTQPLYR GELNEHLGLL G PYIRAEVE DNIMVTFRNQ ASRPYSFYSS LISYEEDQRQ GAEPRKNFVK PNETKTYFWK VQHHMAPTKD EFDCKAWAYF SD VDLEKDV HSGLIGPLLV CHTNTLNPAH GRQVTVQEFA LFFTIFDETK SWYFTENMER NCRAPCNIQM EDPTFKENYR FHA INGYIM DTLPGLVMAQ DQRIRWYLLS MGSNENIHSI HFSGHVFTVR KKEEYKMALY NLYPGVFETV EMLPSKAGIW RVEC LIGEH LHAGMSTLFL VYSNKCQTPL GMASGHIRDF QITASGQYGQ WAPKLARLHY SGSINAWSTK EPFSWIKVDL LAPMI IHGI KTQGARQKFS SLYISQFIIM YSLDGKKWQT YRGNSTGTLM VFFGNVDSSG IKHNIFNPPI IARYIRLHPT HYSIRS TLR MELMGCDLNS CSMPLGMESK AISDAQITAS SYFTNMFATW SPSKARLHLQ GRSNAWRPQV NNPKEWLQVD FQKTMKV TG VTTQGVKSLL TSMYVKEFLI SSSQDGHQWT LFFQNGKVKV FQGNQDSFTP VVNSLDPPLL TRYLRIHPQS WVHQIALR M EVLGCEAQDL Y

UniProtKB: Coagulation factor VIII

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

MacromoleculeName: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 2 / Number of copies: 3 / Formula: NAG
Molecular weightTheoretical: 221.208 Da
Chemical component information

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

-
Macromolecule #3: CALCIUM ION

MacromoleculeName: CALCIUM ION / type: ligand / ID: 3 / Number of copies: 1 / Formula: CA
Molecular weightTheoretical: 40.078 Da

-
Macromolecule #4: COPPER (II) ION

MacromoleculeName: COPPER (II) ION / type: ligand / ID: 4 / Number of copies: 2 / Formula: CU
Molecular weightTheoretical: 63.546 Da
Chemical component information

ChemComp-CU:
COPPER (II) ION

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

Concentration0.1 mg/mL
BufferpH: 7.4
Component:
ConcentrationNameFormula
20.0 mM(4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid)
150.0 mMSodium ChlorideNaCl
5.0 mMCalcium ChlorideCaCl2
GridModel: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 20 sec. / Pretreatment - Atmosphere: AIR
VitrificationCryogen name: ETHANE / Chamber humidity: 95 % / Instrument: FEI VITROBOT MARK IV

-
Electron microscopy

MicroscopeTFS GLACIOS
Image recordingFilm or detector model: FEI FALCON IV (4k x 4k) / Number grids imaged: 1 / Number real images: 4185 / Average electron dose: 55.0 e/Å2 / Details: Cu R1.2/1.3
Electron beamAcceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.5 µm / Nominal defocus min: 1.0 µm / Nominal magnification: 150000
Sample stageCooling holder cryogen: NITROGEN

+
Image processing

Particle selectionNumber selected: 107362
CTF correctionSoftware - Name: cryoSPARC (ver. 5.0.1) / Type: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: NONE
Final reconstructionNumber classes used: 1 / Applied symmetry - Point group: C1 (asymmetric) / Algorithm: BACK PROJECTION / Resolution.type: BY AUTHOR / Resolution: 3.46 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC (ver. 5.0.1) / Number images used: 58291
Initial angle assignmentType: NOT APPLICABLE
Final angle assignmentType: NOT APPLICABLE

-
Atomic model buiding 1

Initial model
PDB IDChain

0451

source_name: AlphaFold, initial_model_type: in silico model

3cdz

source_name: PDB, initial_model_type: experimental model
RefinementSpace: REAL / Protocol: AB INITIO MODEL
Output model

PDB-12jp:
Structural determination of lipid-bound Factor VIII

+
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