[English] 日本語
Yorodumi
- EMDB-16745: Structure of the plasma coagulation Factor XIII A2B2 heterotetram... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-16745
TitleStructure of the plasma coagulation Factor XIII A2B2 heterotetrameric complex.
Map dataLow resolution reconstruction of FactorXIII A2B2 heterotetramer. No symmetry imposed.
Sample
  • Complex: Factor XIII A2B2 heterotetramer
    • Protein or peptide: Coagulation factor XIII A chain
    • Protein or peptide: Coagulation factor XIII B chain
KeywordsFactor XIII heterotetrameric complex / BLOOD CLOTTING
Function / homology
Function and homology information


protein-glutamine gamma-glutamyltransferase / protein-glutamine gamma-glutamyltransferase activity / transferase complex / peptide cross-linking / blood coagulation, fibrin clot formation / Common Pathway of Fibrin Clot Formation / platelet alpha granule lumen / blood coagulation / Platelet degranulation / : ...protein-glutamine gamma-glutamyltransferase / protein-glutamine gamma-glutamyltransferase activity / transferase complex / peptide cross-linking / blood coagulation, fibrin clot formation / Common Pathway of Fibrin Clot Formation / platelet alpha granule lumen / blood coagulation / Platelet degranulation / : / Interleukin-4 and Interleukin-13 signaling / blood microparticle / extracellular space / extracellular region / metal ion binding
Similarity search - Function
: / Transglutaminase, N-terminal / Transglutaminase, C-terminal / Transglutaminase, active site / Protein-glutamine gamma-glutamyltransferase, animal / Transglutaminase, C-terminal domain superfamily / : / Transglutaminase family / Transglutaminase family, C-terminal ig like domain / Transglutaminases active site. ...: / Transglutaminase, N-terminal / Transglutaminase, C-terminal / Transglutaminase, active site / Protein-glutamine gamma-glutamyltransferase, animal / Transglutaminase, C-terminal domain superfamily / : / Transglutaminase family / Transglutaminase family, C-terminal ig like domain / Transglutaminases active site. / Transglutaminase-like superfamily / Transglutaminase/protease-like homologues / Transglutaminase-like / Transglutaminase-like superfamily / Sushi repeat (SCR repeat) / Domain abundant in complement control proteins; SUSHI repeat; short complement-like repeat (SCR) / Sushi/SCR/CCP domain / Sushi/CCP/SCR domain profile. / Sushi/SCR/CCP superfamily / Papain-like cysteine peptidase superfamily / Immunoglobulin E-set / Immunoglobulin-like fold
Similarity search - Domain/homology
Coagulation factor XIII A chain / Coagulation factor XIII B chain
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.04 Å
AuthorsSingh S / Ugurlar D / Hagelueken G / Geyer M / Biswas A
Funding support Germany, 2 items
OrganizationGrant numberCountry
German Research Foundation (DFG)BI 1645/3-1 Germany
German Research Foundation (DFG)SI 2767-1/1 Germany
CitationJournal: Blood / Year: 2025
Title: Cryo-EM structure of the human native plasma coagulation factor XIII complex.
Authors: Sneha Singh / Gregor Hagelueken / Deniz Ugurlar / Samhitha Urs Ramaraje Urs / Amit Sharma / Manoranjan Mahapatra / Friedel Drepper / Diana Imhof / Pitter F Huesgen / Johannes Oldenburg / ...Authors: Sneha Singh / Gregor Hagelueken / Deniz Ugurlar / Samhitha Urs Ramaraje Urs / Amit Sharma / Manoranjan Mahapatra / Friedel Drepper / Diana Imhof / Pitter F Huesgen / Johannes Oldenburg / Matthias Geyer / Arijit Biswas /
Abstract: The structure of human coagulation factor XIII (FXIII), a heterotetrameric plasma protransglutaminase that covalently cross-links preformed fibrin polymers, remains elusive until today. The ...The structure of human coagulation factor XIII (FXIII), a heterotetrameric plasma protransglutaminase that covalently cross-links preformed fibrin polymers, remains elusive until today. The heterotetrameric complex is composed of 2 catalytic FXIII-A and 2 protective FXIII-B subunits. Structural etiology underlying FXIII deficiency has so far been derived from crystallographic structures, all of which are currently available for the FXIII-A2 homodimer only. Here, we present the cryogenic electron microscopy (cryo-EM) structure of a native, human plasma-derived FXIII-A2B2 complex at 2.4 Å resolution. The structure provides detailed information on FXIII subunit interacting interfaces as the 2 subunits interact strongly in plasma. The native FXIII-A2B2 complex reveals a pseudosymmetric heterotetramer of 2 FXIII-B monomers intercalating with a symmetric FXIII-A2 dimer forming a "crown"-like assembly. The symmetry axes of the A2 and B2 homodimers are twisted relative to each other such that Sushi domain 1 interacts with the catalytic core of the A subunit, and Sushi domain 2 with the symmetry related A' subunit, and vice versa. We also report 4 novel mutations in the F13A1 gene encoding the FXIII-A subunit from a cohort of patients with severe FXIII deficiency. Our structure reveals the etiological basis of homozygous and heterozygous pathogenic mutations and explains the conditional dominant negative effects of heterozygous mutations. This atomistic description of complex interfaces is consistent with previous biochemical data and shows a congruence between the structural biochemistry of the FXIII complex and the clinical features of FXIII deficiency.
History
DepositionFeb 21, 2023-
Header (metadata) releaseSep 11, 2024-
Map releaseSep 11, 2024-
UpdateFeb 5, 2025-
Current statusFeb 5, 2025Processing site: PDBe / Status: Released

-
Structure visualization

Supplemental images

emd_16745.png

Downloads & links

-
Map

FileDownload / File: emd_16745.map.gz / Format: CCP4 / Size: 512 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationLow resolution reconstruction of FactorXIII A2B2 heterotetramer. No symmetry imposed.
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.7 Å/pix.
x 512 pix.
= 356.864 Å		0.7 Å/pix.
x 512 pix.
= 356.864 Å		0.7 Å/pix.
x 512 pix.
= 356.864 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.697 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.0344
Minimum - Maximum-0.17571369 - 0.36917463
Average (Standard dev.)0.0001334518 (±0.008664222)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions512512512
Spacing512512512
CellA=B=C: 356.864 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Additional map: Low resolution reconstruction of FactorXIII A2B2 heterotetramer. No...

Fileemd_16745_additional_1.map
AnnotationLow resolution reconstruction of FactorXIII A2B2 heterotetramer. No symmetry imposed.Sharpened map.
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #1

Fileemd_16745_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #2

Fileemd_16745_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : Factor XIII A2B2 heterotetramer

EntireName: Factor XIII A2B2 heterotetramer
Components
  • Complex: Factor XIII A2B2 heterotetramer
    • Protein or peptide: Coagulation factor XIII A chain
    • Protein or peptide: Coagulation factor XIII B chain

-
Supramolecule #1: Factor XIII A2B2 heterotetramer

SupramoleculeName: Factor XIII A2B2 heterotetramer / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Homo sapiens (human)

-
Macromolecule #1: Coagulation factor XIII A chain

MacromoleculeName: Coagulation factor XIII A chain / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO / EC number: protein-glutamine gamma-glutamyltransferase
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 83.365109 KDa
SequenceString: MSETSRTAFG GRRAVPPNNS NAAEDDLPTV ELQGVVPRGV NLQEFLNVTS VHLFKERWDT NKVDHHTDKY ENNKLIVRRG QSFYVQIDF SRPYDPRRDL FRVEYVIGRY PQENKGTYIP VPIVSELQSG KWGAKIVMRE DRSVRLSIQS SPKCIVGKFR M YVAVWTPY ...String:
MSETSRTAFG GRRAVPPNNS NAAEDDLPTV ELQGVVPRGV NLQEFLNVTS VHLFKERWDT NKVDHHTDKY ENNKLIVRRG QSFYVQIDF SRPYDPRRDL FRVEYVIGRY PQENKGTYIP VPIVSELQSG KWGAKIVMRE DRSVRLSIQS SPKCIVGKFR M YVAVWTPY GVLRTSRNPE TDTYILFNPW CEDDAVYLDN EKEREEYVLN DIGVIFYGEV NDIKTRSWSY GQFEDGILDT CL YVMDRAQ MDLSGRGNPI KVSRVGSAMV NAKDDEGVLV GSWDNIYAYG VPPSAWTGSV DILLEYRSSE NPVRYGQCWV FAG VFNTFL RCLGIPARIV TNYFSAHDND ANLQMDIFLE EDGNVNSKLT KDSVWNYHCW NEAWMTRPDL PVGFGGWQAV DSTP QENSD GMYRCGPASV QAIKHGHVCF QFDAPFVFAE VNSDLIYITA KKDGTHVVEN VDATHIGKLI VTKQIGGDGM MDITD TYKF QEGQEEERLA LETALMYGAK KPLNTEGVMK SRSNVDMDFE VENAVLGKDF KLSITFRNNS HNRYTITAYL SANITF YTG VPKAEFKKET FDVTLEPLSF KKEAVLIQAG EYMGQLLEQA SLHFFVTARI NETRDVLAKQ KSTVLTIPEI IIKVRGT QV VGSDMTVTVE FTNPLKETLR NVWVHLDGPG VTRPMKKMFR EIRPNSTVQW EEVCRPWVSG HRKLIASMSS DSLRHVYG E LDVQIQRRPS M

UniProtKB: Coagulation factor XIII A chain

-
Macromolecule #2: Coagulation factor XIII B chain

MacromoleculeName: Coagulation factor XIII B chain / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 75.600594 KDa
SequenceString: MRLKNLTFII ILIISGELYA EEKPCGFPHV ENGRIAQYYY TFKSFYFPMS IDKKLSFFCL AGYTTESGRQ EEQTTCTTEG WSPEPRCFK KCTKPDLSNG YISDVKLLYK IQENMRYGCA SGYKTTGGKD EEVVQCLSDG WSSQPTCRKE HETCLAPELY N GNYSTTQK ...String:
MRLKNLTFII ILIISGELYA EEKPCGFPHV ENGRIAQYYY TFKSFYFPMS IDKKLSFFCL AGYTTESGRQ EEQTTCTTEG WSPEPRCFK KCTKPDLSNG YISDVKLLYK IQENMRYGCA SGYKTTGGKD EEVVQCLSDG WSSQPTCRKE HETCLAPELY N GNYSTTQK TFKVKDKVQY ECATGYYTAG GKKTEEVECL TYGWSLTPKC TKLKCSSLRL IENGYFHPVK QTYEEGDVVQ FF CHENYYL SGSDLIQCYN FGWYPESPVC EGRRNRCPPP PLPINSKIQT HSTTYRHGEI VHIECELNFE IHGSAEIRCE DGK WTEPPK CIEGQEKVAC EEPPFIENGA ANLHSKIYYN GDKVTYACKS GYLLHGSNEI TCNRGKWTLP PECVENNENC KHPP VVMNG AVADGILASY ATGSSVEYRC NEYYLLRGSK ISRCEQGKWS SPPVCLEPCT VNVDYMNRNN IEMKWKYEGK VLHGD LIDF VCKQGYDLSP LTPLSELSVQ CNRGEVKYPL CTRKESKGMC TSPPLIKHGV IISSTVDTYE NGSSVEYRCF DHHFLE GSR EAYCLDGMWT TPPLCLEPCT LSFTEMEKNN LLLKWDFDNR PHILHGEYIE FICRGDTYPA ELYITGSILR MQCDRGQ LK YPRCIPRQST LSYQEPLRT

UniProtKB: Coagulation factor XIII B chain

-
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: FEI FALCON IV (4k x 4k) / Average electron dose: 50.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.8 µm / Nominal defocus min: 0.8 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

+
Image processing

Startup modelType of model: OTHER / Details: Alphafold2 model
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.04 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 20436
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

+
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