[English] 日本語
Yorodumi
- PDB-9zun: Structural insights into the exosite-mediated activation of Facto... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 9zun
TitleStructural insights into the exosite-mediated activation of Factor IX by Factor XIa using cryoEM
Components
  • Coagulation factor IX
  • Coagulation factor XIa heavy chain
  • Coagulation factor XIa light chain
KeywordsBLOOD CLOTTING / Coagulation / Intrinsic Pathway / Complex / Hemophilia / Factor IX / Factor XIa
Function / homology
Function and homology information


Defective F9 secretion / coagulation factor IXa / Defective gamma-carboxylation of F9 / coagulation factor XIa / serine-type aminopeptidase activity / Defective F9 activation / positive regulation of fibrinolysis / Defective factor IX causes thrombophilia / Defective cofactor function of FVIIIa variant / Defective F9 variant does not activate FX ...Defective F9 secretion / coagulation factor IXa / Defective gamma-carboxylation of F9 / coagulation factor XIa / serine-type aminopeptidase activity / Defective F9 activation / positive regulation of fibrinolysis / Defective factor IX causes thrombophilia / Defective cofactor function of FVIIIa variant / Defective F9 variant does not activate FX / : / zymogen activation / plasminogen activation / Protein hydroxylation / 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 / : / serine-type peptidase activity / Golgi lumen / blood coagulation / heparin binding / endopeptidase activity / extracellular matrix / endoplasmic reticulum lumen / serine-type endopeptidase activity / calcium ion binding / proteolysis / : / extracellular exosome / extracellular region / membrane / metal ion binding / identical protein binding / plasma membrane
Similarity search - Function
Apple domain. / Apple domain / APPLE domain / PAN/Apple domain profile. / PAN domain / PAN/Apple domain / Peptidase S1A, coagulation factor VII/IX/X/C/Z / : / Coagulation factor-like, Gla domain superfamily / Coagulation Factor Xa inhibitory site ...Apple domain. / Apple domain / APPLE domain / PAN/Apple domain profile. / PAN domain / PAN/Apple domain / Peptidase S1A, coagulation factor VII/IX/X/C/Z / : / Coagulation factor-like, Gla domain superfamily / Coagulation Factor Xa inhibitory site / EGF-like domain / EGF-type aspartate/asparagine hydroxylation site / EGF-like calcium-binding, conserved site / Calcium-binding EGF-like domain signature. / Aspartic acid and asparagine hydroxylation site. / Vitamin K-dependent carboxylation/gamma-carboxyglutamic (GLA) domain / EGF-like calcium-binding domain / Calcium-binding EGF-like domain / 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. / Epidermal growth factor-like domain. / EGF-like domain profile. / EGF-like domain signature 1. / EGF-like domain signature 2. / EGF-like domain / Serine proteases, trypsin family, histidine active site / Serine proteases, trypsin family, serine active site / Serine proteases, trypsin family, histidine active site. / Serine proteases, trypsin family, serine active site. / Peptidase S1A, chymotrypsin family / Serine proteases, trypsin domain profile. / Trypsin-like serine protease / Serine proteases, trypsin domain / Trypsin / Peptidase S1, PA clan, chymotrypsin-like fold / Peptidase S1, PA clan
Similarity search - Domain/homology
Coagulation factor IX / Coagulation factor XI
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.55 Å
AuthorsMohammed, B.M.
Funding support United States, 5items
OrganizationGrant numberCountry
Other privateDoisy Fund of the Edward A. Doisy Department of Biochemistry and Molecular Biology
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 insights into the exosite-mediated activation of Factor IX by Factor XIa using cryo-EM.
Authors: Bassem M Mohammed / Samantha Deavila / Tristan Friet / Isabella Dattilio /
Abstract: BACKGROUND: Factor XI (FXI) occupies a unique and clinically significant niche, bridging the tissue factor-driven and contact-driven coagulation pathways. Irrespective of the trigger, activated ...BACKGROUND: Factor XI (FXI) occupies a unique and clinically significant niche, bridging the tissue factor-driven and contact-driven coagulation pathways. Irrespective of the trigger, activated factor XI (FXIa) contributes to clotting by activating factor IX (FIX). Biochemical studies established that this reaction requires the membrane-binding FIX-Gla domain to engage an exosite on the FXIa Apple 3 (A3) domain, that only become available upon FXI activation. Structural data for FXIa, FIX, FIXaβ, and the FXIa:FIX complex are lacking; current understanding relies on zymogen FXI crystal structures and homology modeling of FXIa after kallikrein.
OBJECTIVES: Elucidate the high-resolution structure of FXIa in functionally relevant conformation in complex with FIX.
METHODS: We utilized cryogenic electron microscopy (cryo-EM) to determine the structures of human FXIa in complex with its full-length substrate, FIX, and activated product, FIXaβ.
RESULTS: We report the first cryo-EM structures of FXIa in complex with its substrate, FIX, and activated FIX (FIXaβ). The structures capture a functionally relevant conformational change in the ...RESULTS: We report the first cryo-EM structures of FXIa in complex with its substrate, FIX, and activated FIX (FIXaβ). The structures capture a functionally relevant conformational change in the FXIa catalytic domain and reveals the first view of the entire FIX and FIXaβ. Critically, we visualize the FIX-Gla domain precisely docked to the FXIa-A3 exosite on both subunits of the FXIa dimer. We also define the first step of proteolysis, visualizing the FIX Arg145 inserted into the primary specificity pocket of FXIa.
CONCLUSIONS: The structures define the full FXIa:FIX interface providing a structural template for understanding the sequential activation of FIX and for developing a new class of selective ...CONCLUSIONS: The structures define the full FXIa:FIX interface providing a structural template for understanding the sequential activation of FIX and for developing a new class of selective allosteric antithrombotic agents.
History
DepositionDec 24, 2025Deposition site: RCSB / Processing site: RCSB
Revision 1.0Sep 9, 2026Provider: repository / Type: Initial release
Revision 1.0Sep 9, 2026Data content type: EM metadata / Data content type: EM metadata / Provider: repository / Type: Initial release

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Coagulation factor XIa heavy chain
B: Coagulation factor XIa light chain
C: Coagulation factor IX
hetero molecules


Theoretical massNumber of molelcules
Total (without water)116,31215
Polymers115,1073
Non-polymers1,20512
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_5551

-
Components

#1: Protein Coagulation factor XIa heavy chain


Mass: 41262.098 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Details: Activated Recombinant Factor XI Ser557Ala. The molecule is a dimer that is disulphide linked at Cys321. During activation the bond at R369 is cleaved on each subunit to give a two chain ...Details: Activated Recombinant Factor XI Ser557Ala. The molecule is a dimer that is disulphide linked at Cys321. During activation the bond at R369 is cleaved on each subunit to give a two chain molecule. only one monomer is solved here and is composed of a heavy chain (A) and light (B)
Source: (gene. exp.) Homo sapiens (human) / Gene: F11 / Plasmid: pDest40 / Cell line (production host): HEK 293 cells / Production host: Homo sapiens (human) / References: UniProt: P03951, coagulation factor XIa
#2: Antibody Coagulation factor XIa light chain


Mass: 26686.352 Da / Num. of mol.: 1 / Mutation: S557A
Source method: isolated from a genetically manipulated source
Details: Activated Recombinant Factor XI Ser557Ala. The molecule is a dimer that is disulphide linked at Cys321. During activation the bond at R369 is cleaved on each subunit to give a two chain ...Details: Activated Recombinant Factor XI Ser557Ala. The molecule is a dimer that is disulphide linked at Cys321. During activation the bond at R369 is cleaved on each subunit to give a two chain molecule. only one monomer is solved here and is composed of a heavy chain (A) and light (B)
Source: (gene. exp.) Homo sapiens (human) / Gene: F11 / Plasmid: pDest40 / Cell line (production host): HEK 293 cells / Production host: Homo sapiens (human) / References: UniProt: P03951
#3: Protein Coagulation factor IX / Christmas factor / Plasma thromboplastin component / PTC


Mass: 47158.219 Da / Num. of mol.: 1 / Source method: isolated from a natural source
Details: CGU are Glu residues with post-translational modification adding a carboxyl group to the gamma carbon of Glu
Source: (natural) Homo sapiens (human) / Plasmid details: Human Plasma / Tissue: Plasma / References: UniProt: P00740, coagulation factor IXa
#4: 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.: 4
Source method: isolated from a genetically manipulated source
Formula: C8H15NO6 / Feature type: SUBJECT OF INVESTIGATION
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
#5: Chemical
ChemComp-CA / CALCIUM ION


Mass: 40.078 Da / Num. of mol.: 8 / Source method: obtained synthetically / Formula: Ca / Feature type: SUBJECT OF INVESTIGATION
Compound detailsIn vivo, the proteins are made in the liver, and secreted in blood.
Has ligand of interestY
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

Component
IDNameTypeDetails (eV)Entity IDParent-IDSource
1Complex of Factor XIa (FXIa) with Factor IX (FIX).COMPLEXFXIa is a dimer and binds 2 FIX molecules. Factor XIa used in this preparation is recombinant FXIa with a Ser557Ala mutation (mature protein numbering). recombinant protein is made as a zymogen that is activated. The activation involves cleavage after residue Arg369 of FXI to give FXIa#30MULTIPLE SOURCES
2Activated coagulation Factor XI (FXIa)COMPLEXMade from recombinant FXI that was activated to give FXIa. Has a Ser557Ala mutation to render it catalytically dead.#11RECOMBINANT
3Coagulation Factor IX (FIX)COMPLEXPurified from human plasma#31NATURAL
Molecular weight
IDEntity assembly-IDValue (°)Experimental value
11NO
210.160 MDaYES
310.057 MDaYES
Source (natural)
IDEntity assembly-IDOrganismNcbi tax-IDOrganTissue
21Homo sapiens (human)9606liverPlasma
32Homo sapiens (human)9606liverPlasma
43Homo sapiens (human)9606liverPlasma
Source (recombinant)Organism: Homo sapiens (human) / Cell: HEK293 / Plasmid: pDest40
Buffer solution
IDSpecimen-IDpH
117.4
227.4
Buffer component
IDConc.NameFormulaBuffer-ID
120 mMHEPES1
2150 mMSodium ChlorideNaCl1
35 mMCalcium chlorideCaCl21
420 mMHEPES2
5150 mMSodium ChlorideNaCl2
65 mMCalcium ChlorideCaCl22
Specimen
IDConc. (mg/ml)Experiment-IDEmbedding appliedShadowing appliedStaining appliedVitrification applied
10.11NONONOYES
20.11NONONOYES
Specimen support
IDSpecimen-IDGrid materialGrid mesh size (divisions/in.)Grid type
11COPPER300Quantifoil R1.2/1.3
22GOLD300Quantifoil R1.2/1.3
Vitrification
IDInstrumentCryogen nameHumidity (%)Specimen-IDChamber temperature (K)Entry-ID
1FEI VITROBOT MARK IVETHANE951277.159ZUN
2FEI VITROBOT MARK IVETHANE952277.159ZUN

-
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: 150000 X / Nominal defocus max: 2400 nm / Nominal defocus min: 1000 nm / Cs: 2.7 mm
Specimen holderCryogen: NITROGEN
Image recording
IDImaging-IDElectron dose (e/Å2)Film or detector modelNum. of grids imagedNum. of real imagesDetails (eV)
1160FEI FALCON IV (4k x 4k)14662
2157.2FEI FALCON IV (4k x 4k)1183230 degree tilt
3152.5FEI FALCON IV (4k x 4k)11297
4152.5FEI FALCON IV (4k x 4k)1817
5150FEI FALCON IV (4k x 4k)12789
Image scans
WidthHeightIDImage recording-IDEntry-ID
40964096119ZUN
40964096229ZUN
40964096339ZUN
40964096449ZUN
40964096559ZUN

-
Processing

EM software
IDNameVersionCategoryImage processing-ID
1cryoSPARC4.7.1particle selection1
2EPUimage acquisition
4cryoSPARC4.7.1CTF correction1
7UCSF ChimeraX1.1model fitting
9PHENIX1.21.2_5419model refinement
10Coot0.9.8.95model refinement
13cryoSPARC4.7.1classification1
14cryoSPARC4.7.13D reconstruction1
15cryoSPARC4.7.1particle selection2
16cryoSPARC4.7.1CTF correction2
19cryoSPARC4.7.1classification2
20cryoSPARC4.7.13D reconstruction2
Image processing
IDImage recording-ID
11
22
CTF correction
IDEM image processing-IDType
11PHASE FLIPPING AND AMPLITUDE CORRECTION
22PHASE FLIPPING AND AMPLITUDE CORRECTION
Particle selection
IDImage processing-IDNum. of particles selected
11682170
22682170
Symmetry
IDImage processing-IDEntry-IDPoint symmetry
119ZUNC1 (asymmetric)
219ZUNC1 (asymmetric)
3D reconstruction

Algorithm: BACK PROJECTION / Entry-ID: 9ZUN / Num. of class averages: 1 / Num. of particles: 121893 / Resolution: 3.55 Å / Resolution method: FSC 0.143 CUT-OFF / Symmetry type: POINT

IDImage processing-ID
11
21
32
42
Atomic model buildingProtocol: OTHER / Space: REAL / Details: Combined Rigid fit, backbone trace, and ab-initio
Atomic model building

3D fitting-ID: 1

IDPDB-IDAccession codeDetails (eV)Initial refinement model-IDSource nameType
16I58

6i58

6I58Factor XI1PDBexperimental model
21NL0

1nl0

1NL0Factor IX - Gla2PDBexperimental model
3AF-F2RM35-F1-v4Factor IX3AlphaFoldin silico model
49ZqY

9zqy

9ZqYRelated entry to this deposition built by ab-initio4PDBexperimental model

+
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