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- EMDB-56398: Cryo-EM structure of native ITIH4 with 12A12 F(ab) -

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Basic information

Entry
Database: EMDB / ID: EMD-56398
TitleCryo-EM structure of native ITIH4 with 12A12 F(ab)
Map data
Sample
  • Complex: Inter-alpha-trypsin inhibitor heavy chain 4
    • Protein or peptide: Isoform 3 of Inter-alpha-trypsin inhibitor heavy chain H4
    • Protein or peptide: 12A12 mAb F(ab) heavy chain
    • Protein or peptide: 12A12 mAb F(ab) light chain
KeywordsProtease inhibitor / plasma protein / complement / coagulation / contact cascade / IMMUNE SYSTEM
Function / homology
Function and homology information


hyaluronan metabolic process / platelet dense granule lumen / endopeptidase inhibitor activity / acute-phase response / response to cytokine / serine-type endopeptidase inhibitor activity / Platelet degranulation / blood microparticle / extracellular matrix / extracellular exosome ...hyaluronan metabolic process / platelet dense granule lumen / endopeptidase inhibitor activity / acute-phase response / response to cytokine / serine-type endopeptidase inhibitor activity / Platelet degranulation / blood microparticle / extracellular matrix / extracellular exosome / extracellular region / plasma membrane
Similarity search - Function
Inter-alpha-trypsin inhibitor heavy chain, C-terminal / : / Inter-alpha-trypsin inhibitor heavy chain C-terminus / VIT domain / Vault protein inter-alpha-trypsin domain / VIT domain profile. / Vault protein Inter-alpha-Trypsin domain / von Willebrand factor type A domain / VWFA domain profile. / von Willebrand factor (vWF) type A domain ...Inter-alpha-trypsin inhibitor heavy chain, C-terminal / : / Inter-alpha-trypsin inhibitor heavy chain C-terminus / VIT domain / Vault protein inter-alpha-trypsin domain / VIT domain profile. / Vault protein Inter-alpha-Trypsin domain / von Willebrand factor type A domain / VWFA domain profile. / von Willebrand factor (vWF) type A domain / von Willebrand factor, type A / von Willebrand factor A-like domain superfamily
Similarity search - Domain/homology
Inter-alpha-trypsin inhibitor heavy chain H4
Similarity search - Component
Biological speciesHomo sapiens (human) / Mus musculus (house mouse)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.1 Å
AuthorsJoergensen MH / Andersen GR
Funding support Denmark, 1 items
OrganizationGrant numberCountry
Novo Nordisk FoundationNNF25OC0101234 Denmark
CitationJournal: To Be Published
Title: The plasma protease inhibitor ITIH4 forms oligomeric complexes and senses broader, proteolytic activity
Authors: Joergensen MH / Andersen GR
History
DepositionJan 15, 2026-
Header (metadata) releaseSep 23, 2026-
Map releaseSep 23, 2026-
UpdateSep 23, 2026-
Current statusSep 23, 2026Processing site: PDBe / Status: Released

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Structure visualization

Supplemental images

emd_56398.png

Downloads & links

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Map

FileDownload / File: emd_56398.map.gz / Format: CCP4 / Size: 30.5 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.25 Å/pix.
x 200 pix.
= 250. Å		1.25 Å/pix.
x 200 pix.
= 250. Å		1.25 Å/pix.
x 200 pix.
= 250. Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.25 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.167
Minimum - Maximum-0.24942313 - 0.554037
Average (Standard dev.)0.0012136308 (±0.021483017)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions200200200
Spacing200200200
CellA=B=C: 250.0 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #2

Fileemd_56398_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: #1

Fileemd_56398_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : Inter-alpha-trypsin inhibitor heavy chain 4

EntireName: Inter-alpha-trypsin inhibitor heavy chain 4
Components
  • Complex: Inter-alpha-trypsin inhibitor heavy chain 4
    • Protein or peptide: Isoform 3 of Inter-alpha-trypsin inhibitor heavy chain H4
    • Protein or peptide: 12A12 mAb F(ab) heavy chain
    • Protein or peptide: 12A12 mAb F(ab) light chain

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Supramolecule #1: Inter-alpha-trypsin inhibitor heavy chain 4

SupramoleculeName: Inter-alpha-trypsin inhibitor heavy chain 4 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: Isoform 3 of Inter-alpha-trypsin inhibitor heavy chain H4

MacromoleculeName: Isoform 3 of Inter-alpha-trypsin inhibitor heavy chain H4
type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 100.793141 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MKPPRPVRTC SKVLVLLSLL AIHQTTTAEK NGIDIYSLTV DSRVSSRFAH TVVTSRVVNR ANTVQEATFQ MELPKKAFIT NFSMIIDGM TYPGIIKEKA EAQAQYSAAV AKGKSAGLVK ATGRNMEQFQ VSVSVAPNAK ITFELVYEEL LKRRLGVYEL L LKVRPQQL ...String:
MKPPRPVRTC SKVLVLLSLL AIHQTTTAEK NGIDIYSLTV DSRVSSRFAH TVVTSRVVNR ANTVQEATFQ MELPKKAFIT NFSMIIDGM TYPGIIKEKA EAQAQYSAAV AKGKSAGLVK ATGRNMEQFQ VSVSVAPNAK ITFELVYEEL LKRRLGVYEL L LKVRPQQL VKHLQMDIHI FEPQGISFLE TESTFMTNQL VDALTTWQNK TKAHIRFKPT LSQQQKSPEQ QETVLDGNLI IR YDVDRAI SGGSIQIENG YFVHYFAPEG LTTMPKNVVF VIDKSGSMSG RKIQQTREAL IKILDDLSPR DQFNLIVFST EAT QWRPSL VPASAENVNK ARSFAAGIQA LGGTNINDAM LMAVQLLDSS NQEERLPEGS VSLIILLTDG DPTVGETNPR SIQN NVREA VSGRYSLFCL GFGFDVSYAF LEKLALDNGG LARRIHEDSD SALQLQDFYQ EVANPLLTAV TFEYPSNAVE EVTQN NFRL LFKGSEMVVA GKLQDRGPDV LTATVSGKLP TQNITFQTES SVAEQEAEFQ SPKYIFHNFM ERLWAYLTIQ QLLEQT VSA SDADQQALRN QALNLSLAYS FVTPLTSMVV TKPDDQEQSQ VAEKPMEGES RNRNVHSAGA AGSRMNFRPG VLSSRQL GL PGPPDVPDHA AYHPFRRLAI LPASAPPATS NPDPAVSRVM NMKIEETTMT TQTPAPIQAP SAILPLPGQS VERLCVDP R HRQGPVNLLS DPEQGVEVTG QYEREKAGFS WIEVTFKNPL VWVHASPEHV VVTRNRRSSA YKWKETLFSV MPGLKMTMD KTGLLLLSDP DKVTIGLLFW DGRGEGLRLL LRDTDRFSSH VGGTLGQFYQ EVLWGSPAAS DDGRRTLRVQ GNDHSATRER RLDYQEGPP GVEISCWSVE LHHHHHH

UniProtKB: Inter-alpha-trypsin inhibitor heavy chain H4

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Macromolecule #2: 12A12 mAb F(ab) heavy chain

MacromoleculeName: 12A12 mAb F(ab) heavy chain / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Mus musculus (house mouse)
Molecular weightTheoretical: 24.204084 KDa
SequenceString: EVQLQQSGPE LVKPGASVKM SCKASGYTFK TYLMHWVKQK PGQGLEWIGY IDPYNDGTKY NEKFKGKATL TSDKSSSTAY MELSSLTSE DSAVYYCAKD YGYDTYWGQG TLVTVSAAKT TPPSVYPLAP GCGDTTGSSV TLGCLVKGYF PESVTVTWNS G SLSSSVHT ...String:
EVQLQQSGPE LVKPGASVKM SCKASGYTFK TYLMHWVKQK PGQGLEWIGY IDPYNDGTKY NEKFKGKATL TSDKSSSTAY MELSSLTSE DSAVYYCAKD YGYDTYWGQG TLVTVSAAKT TPPSVYPLAP GCGDTTGSSV TLGCLVKGYF PESVTVTWNS G SLSSSVHT FPALLQSGLY TMSSSVTVPS STWPSQTVTC SVAHPASSTT VDKKLEPSGP ISTINPCPP

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Macromolecule #3: 12A12 mAb F(ab) light chain

MacromoleculeName: 12A12 mAb F(ab) light chain / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Mus musculus (house mouse)
Molecular weightTheoretical: 23.693213 KDa
SequenceString: DIQMTQSPSS LSASLGGKVT ITCKASQDIN KYIAWYQHKP GKGPRLLIHY TSTLHPDIPS RFSGSGSGRD YSFSISNLEP EDIATYYCL QYDNLWTFGG GTKLEIKRAD AAPTVSIFPP SSEQLTSGGA SVVCFLNNFY PKDINVKWKI DGSERQNGVL N SWTDQDSK ...String:
DIQMTQSPSS LSASLGGKVT ITCKASQDIN KYIAWYQHKP GKGPRLLIHY TSTLHPDIPS RFSGSGSGRD YSFSISNLEP EDIATYYCL QYDNLWTFGG GTKLEIKRAD AAPTVSIFPP SSEQLTSGGA SVVCFLNNFY PKDINVKWKI DGSERQNGVL N SWTDQDSK DSTYSMSSTL TLTKDEYERH NSYTCEATHK TSTSPIVKSF NRNEC

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 7.5
VitrificationCryogen name: ETHANE / Instrument: FEI VITROBOT MARK IV

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Electron microscopy

MicroscopeTFS GLACIOS
Image recordingFilm or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 70.0 e/Å2
Electron beamAcceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.7000000000000001 µm

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Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.1 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC (ver. 4.5) / Number images used: 168764
Initial angle assignmentType: RANDOM ASSIGNMENT
Final angle assignmentType: MAXIMUM LIKELIHOOD

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