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- PDB-36jl: Coagulation factor VIII, full-length, membrane-bound, on Ptd-chol... -

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Basic information

Entry
Database: PDB / ID: 36jl
TitleCoagulation factor VIII, full-length, membrane-bound, on Ptd-choline : Ptd-serine 75:25 vesicles
ComponentsCoagulation factor VIII
KeywordsMEMBRANE PROTEIN / coagulation factor VIII / discoidin / phosphatidylserine / liposome
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 / Amplification and propagation of coagulation cascade / Cargo concentration in the ER / Initiation of coagulation cascade ...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 / Amplification and propagation of coagulation cascade / Cargo concentration in the ER / Initiation of coagulation cascade / COPII-coated ER to Golgi transport vesicle / Defective factor IX causes thrombophilia / Defective cofactor function of FVIIIa variant / Defective F9 variant does not activate FX / COPII-mediated vesicle transport / Regulation of clotting cascade / Defective F8 cleavage by thrombin / endoplasmic reticulum-Golgi intermediate compartment membrane / platelet alpha granule lumen / 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 / Multicopper oxidase, C-terminal / Multicopper oxidase / Coagulation factors 5/8 type C domain (FA58C) profile. ...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 / Multicopper oxidase, C-terminal / Multicopper oxidase / Coagulation factors 5/8 type C domain (FA58C) profile. / 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
COPPER (I) ION / PHOSPHOSERINE / Coagulation factor VIII
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.15 Å
AuthorsKolyadko, V.N. / Pumroy, R.A. / Moiseenkova-Bell, V.Y. / Krishnaswamy, S.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI)P01HL139420 United States
CitationJournal: Proc Natl Acad Sci U S A / Year: 2026
Title: Structural basis for membrane binding by coagulation factors V and VIII and their specificity for phosphatidylserine-containing membranes.
Authors: Vladimir N Kolyadko / Ruth A Pumroy / Vera Y Moiseenkova-Bell / Sriram Krishnaswamy /
Abstract: Phosphatidylserine on the surface of activated cells serves as a signal for coagulation factor binding and the membrane-dependent assembly of enzyme complexes that drive the accelerated host response ...Phosphatidylserine on the surface of activated cells serves as a signal for coagulation factor binding and the membrane-dependent assembly of enzyme complexes that drive the accelerated host response to vascular damage. Here, we use single-particle cryo-EM of liposome-bound proteins to establish common mechanisms utilized by coagulation factors V and VIII for membrane binding and phospholipid specificity. The interface between these peripheral proteins and the membrane shows contacts between the discoidin C1 and C2 domains and the interfacial phospholipid headgroup region of the membrane bilayer. There is no evidence for the insertion of membrane-contacting protein loops into the membrane core. This refutes previous models of high affinity protein binding by insertion into the hydrophobic core of the membrane. We also resolve density for the headgroup of phosphatidylserine bound to conserved pockets within the C1 and C2 domains. These single binding pockets in each C domain highlight the network of putative hydrogen bonds that contribute to binding specificity for phosphatidylserine. Our results now provide a high-resolution structural view of the protein-membrane interface for these coagulation proteins and highlight the utility of using liposomes as near-physiologic membrane mimetics in structural studies. The principles established in this work may also apply to other biological systems wherein function is regulated by reversible membrane binding.
History
DepositionJun 14, 2026Deposition site: RCSB / Processing site: RCSB
Revision 1.0Sep 16, 2026Provider: repository / Type: Initial release
Revision 1.0Sep 16, 2026Data content type: EM metadata / Data content type: EM metadata / Provider: repository / Type: Initial release

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

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Assembly

Deposited unit
A: Coagulation factor VIII
hetero molecules


Theoretical massNumber of molelcules
Total (without water)266,6569
Polymers265,0611
Non-polymers1,5958
Water181
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1

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Components

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Protein / Sugars , 2 types, 3 molecules A

#1: Protein Coagulation factor VIII / Antihemophilic factor / AHF / Procoagulant component


Mass: 265061.062 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: F8, F8C / Cell line (production host): BHK / Production host: Mesocricetus auratus (golden hamster) / References: UniProt: P00451
#2: Sugar ChemComp-NAG / 2-acetamido-2-deoxy-beta-D-glucopyranose / N-acetyl-beta-D-glucosamine / 2-acetamido-2-deoxy-beta-D-glucose / 2-acetamido-2-deoxy-D-glucose / 2-acetamido-2-deoxy-glucose / N-ACETYL-D-GLUCOSAMINE


Type: D-saccharide, beta linking / Mass: 221.208 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C8H15NO6
IdentifierTypeProgram
DGlcpNAcbCONDENSED IUPAC CARBOHYDRATE SYMBOLGMML 1.0
N-acetyl-b-D-glucopyranosamineCOMMON NAMEGMML 1.0
b-D-GlcpNAcIUPAC CARBOHYDRATE SYMBOLPDB-CARE 1.0
GlcNAcSNFG CARBOHYDRATE SYMBOLGMML 1.0

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Non-polymers , 5 types, 7 molecules

#3: Chemical ChemComp-CA / CALCIUM ION


Mass: 40.078 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Ca / Feature type: SUBJECT OF INVESTIGATION
#4: Chemical ChemComp-CU1 / COPPER (I) ION


Mass: 63.546 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Cu / Feature type: SUBJECT OF INVESTIGATION
#5: Chemical ChemComp-SEP / PHOSPHOSERINE / PHOSPHONOSERINE


Type: L-peptide linking / Mass: 185.072 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C3H8NO6P / Feature type: SUBJECT OF INVESTIGATION
#6: Chemical ChemComp-CPS / 3-[(3-CHOLAMIDOPROPYL)DIMETHYLAMMONIO]-1-PROPANESULFONATE / CHAPS


Mass: 614.877 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C32H58N2O7S / Comment: detergent*YM
#7: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Formula: H2O

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Details

Has ligand of interestY
Has protein modificationY

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Experimental details

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Experiment

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

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Sample preparation

ComponentName: Coagulation factor VIII, glycosylated, bound to calcium (II) and copper (I), and to phosphatidyl-L-serine headgroups in small unilamellar vesicles
Type: COMPLEX
Details: Small unilamellar vesicles are composed of a mixture of phospholipids (phosphatidylcholine : phosphatidylserine 75:25)
Entity ID: #1 / Source: RECOMBINANT
Molecular weightValue: 0.33 MDa / Experimental value: YES
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Mesocricetus auratus (golden hamster)
Buffer solutionpH: 7.5
Buffer component
IDConc.NameFormulaBuffer-ID
120 mMHEPES1
2150 mMsodium chlorideNaCl1
35 mMcalcium chlorideCaCl21
40.2 mMCHAPS1
SpecimenConc.: 0.1 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
Details: Protein is mixed with prepared small unilamellar vesicles
Specimen supportGrid material: GOLD / Grid mesh size: 300 divisions/in. / Grid type: UltrAuFoil R0./1
VitrificationInstrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 293 K

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Electron microscopy imaging

MicroscopyModel: TFS GLACIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal magnification: 130000 X / Nominal defocus max: 2500 nm / Nominal defocus min: 1000 nm / Cs: 2.7 mm
Specimen holderCryogen: NITROGEN
Image recordingElectron dose: 39.64 e/Å2 / Film or detector model: TFS FALCON 4i (4k x 4k) / Num. of grids imaged: 1 / Num. of real images: 9197
EM imaging opticsEnergyfilter slit width: 20 eV

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Processing

EM software
IDNameVersionCategory
1cryoSPARCparticle selection
2Topazparticle selection
3PHENIX1.20.1_4487model refinement
14RELION53D reconstruction
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 3.15 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 212413 / Symmetry type: POINT
Atomic model buildingProtocol: AB INITIO MODEL
RefinementHighest resolution: 3.15 Å / Cross valid method: NONE
Stereochemistry target values: REAL-SPACE (WEIGHTED MAP SUM AT ATOM CENTERS)

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