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- EMDB-62028: Cryo-EM structure of TMPRSS2 in complex with Fab fragments of 752... -

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Basic information

Entry
Database: EMDB / ID: EMD-62028
TitleCryo-EM structure of TMPRSS2 in complex with Fab fragments of 752 mAb and 2228 mAb
Map data
Sample
  • Complex: TMPRSS2 ECD and Fab fragments complex
    • Complex: TMPRSS2
      • Protein or peptide: Transmembrane protease serine 2
    • Complex: Fab 752
      • Protein or peptide: Fab 752 light chain
      • Protein or peptide: Fab 752 heavy chain
    • Complex: Fab 2228
      • Protein or peptide: Fab 2228 light chain
      • Protein or peptide: Fab 2228 heavy chain
KeywordsHYDROLASE / IMMUNE SYSTEM / MEMBRANE PROTEIN
Function / homology
Function and homology information


transmembrane protease serine 2 / protein autoprocessing / Attachment and Entry / serine-type peptidase activity / viral translation / Induction of Cell-Cell Fusion / entry receptor-mediated virion attachment to host cell / Attachment and Entry / positive regulation of viral entry into host cell / serine-type endopeptidase activity ...transmembrane protease serine 2 / protein autoprocessing / Attachment and Entry / serine-type peptidase activity / viral translation / Induction of Cell-Cell Fusion / entry receptor-mediated virion attachment to host cell / Attachment and Entry / positive regulation of viral entry into host cell / serine-type endopeptidase activity / proteolysis / extracellular exosome / extracellular region / nucleoplasm / plasma membrane
Similarity search - Function
Scavenger receptor cysteine-rich domain / SRCR domain profile. / SRCR-like domain superfamily / Scavenger receptor Cys-rich / SRCR domain / Low-density lipoprotein (LDL) receptor class A, conserved site / LDL-receptor class A (LDLRA) domain signature. / LDL-receptor class A (LDLRA) domain profile. / Low-density lipoprotein receptor domain class A / Low-density lipoprotein (LDL) receptor class A repeat ...Scavenger receptor cysteine-rich domain / SRCR domain profile. / SRCR-like domain superfamily / Scavenger receptor Cys-rich / SRCR domain / Low-density lipoprotein (LDL) receptor class A, conserved site / LDL-receptor class A (LDLRA) domain signature. / LDL-receptor class A (LDLRA) domain profile. / Low-density lipoprotein receptor domain class A / Low-density lipoprotein (LDL) receptor class A repeat / LDL receptor-like superfamily / Serine proteases, trypsin family, histidine active site / Serine proteases, trypsin family, serine active site / Serine proteases, trypsin family, histidine active site. / Peptidase S1A, chymotrypsin family / Serine proteases, trypsin family, serine active site. / 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
Transmembrane protease serine 2
Similarity search - Component
Biological speciesHomo sapiens (human) / Mus musculus (house mouse)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.15 Å
AuthorsKatsura K / Hisano T / Matsumoto T / Shirouzu M
Funding support Japan, 1 items
OrganizationGrant numberCountry
Japan Agency for Medical Research and Development (AMED) Japan
CitationJournal: Iscience / Year: 2025
Title: Monoclonal antibodies against human TMPRSS2 prevent infection by any SARS-CoV-2 variant
Authors: Harada M / Matsumoto T / Yamamoto M / Goda J / Idei A / Ohtaki K / Kojima N / Yoneda N / Miyauchi K / Katsura K / Ikeda M / Hanada K / Ishizuka-Katsura Y / Hosaka T / Hisano T / Kaizuka T / ...Authors: Harada M / Matsumoto T / Yamamoto M / Goda J / Idei A / Ohtaki K / Kojima N / Yoneda N / Miyauchi K / Katsura K / Ikeda M / Hanada K / Ishizuka-Katsura Y / Hosaka T / Hisano T / Kaizuka T / Yamamoto T / Matsuda M / Nakayama M / Sugimoto-Ishige A / Sakuma M / Hashimoto R / Takayama K / Nakayama M / Nguyen CT / Ishigaki H / Itoh Y / Hashizume Y / Yoshida M / Kawaguchi Y / Takeda M / Koseki H / Shirouzu M / Inoue JI / Saito T
History
DepositionOct 20, 2024-
Header (metadata) releaseOct 15, 2025-
Map releaseOct 15, 2025-
UpdateOct 15, 2025-
Current statusOct 15, 2025Processing site: PDBj / Status: Released

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Structure visualization

Supplemental images

emd_62028.png

Downloads & links

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Map

FileDownload / File: emd_62028.map.gz / Format: CCP4 / Size: 103 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesX (Sec.)Y (Row.)Z (Col.)
0.83 Å/pix.
x 300 pix.
= 248.55 Å		0.83 Å/pix.
x 300 pix.
= 248.55 Å		0.83 Å/pix.
x 300 pix.
= 248.55 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.8285 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 8.0
Minimum - Maximum-66.0411 - 76.829880000000003
Average (Standard dev.)-0.00000000001033 (±1.0)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderZYX
Origin000
Dimensions300300300
Spacing300300300
CellA=B=C: 248.54999 Å
α=β=γ: 90.0 °

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Supplemental data

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Mask #1

Fileemd_62028_msk_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: #2

Fileemd_62028_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_62028_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 : TMPRSS2 ECD and Fab fragments complex

EntireName: TMPRSS2 ECD and Fab fragments complex
Components
  • Complex: TMPRSS2 ECD and Fab fragments complex
    • Complex: TMPRSS2
      • Protein or peptide: Transmembrane protease serine 2
    • Complex: Fab 752
      • Protein or peptide: Fab 752 light chain
      • Protein or peptide: Fab 752 heavy chain
    • Complex: Fab 2228
      • Protein or peptide: Fab 2228 light chain
      • Protein or peptide: Fab 2228 heavy chain

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Supramolecule #1: TMPRSS2 ECD and Fab fragments complex

SupramoleculeName: TMPRSS2 ECD and Fab fragments complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all

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Supramolecule #2: TMPRSS2

SupramoleculeName: TMPRSS2 / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1
Source (natural)Organism: Homo sapiens (human)

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Supramolecule #3: Fab 752

SupramoleculeName: Fab 752 / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2-#3
Source (natural)Organism: Mus musculus (house mouse)

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Supramolecule #4: Fab 2228

SupramoleculeName: Fab 2228 / type: complex / ID: 4 / Parent: 1 / Macromolecule list: #4-#5
Source (natural)Organism: Mus musculus (house mouse)

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Macromolecule #1: Transmembrane protease serine 2

MacromoleculeName: Transmembrane protease serine 2 / type: protein_or_peptide / ID: 1
Details: The sequence responsible for TMPRSS2 autoactivation (250SSRQSR255) was substituted with the 6 residues containing an enterokinase cleavage site.
Number of copies: 1 / Enantiomer: LEVO / EC number: transmembrane protease serine 2
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 43.250609 KDa
Recombinant expressionOrganism: Baculovirus transfer vector pFASTBAC1
SequenceString: GMGSKCSNSG IECDSSGTCI NPSNWCDGVS HCPGGEDENR CVRLYGPNFI LQVYSSQRKS WHPVCQDDWN ENYGRAACRD MGYKNNFYS SQGIVDDSGS TSFMKLNTSA GNVDIYKKLY HSDACSSKAV VSLRCIACGV NLNDDDDDKI VGGESALPGA W PWQVSLHV ...String:
GMGSKCSNSG IECDSSGTCI NPSNWCDGVS HCPGGEDENR CVRLYGPNFI LQVYSSQRKS WHPVCQDDWN ENYGRAACRD MGYKNNFYS SQGIVDDSGS TSFMKLNTSA GNVDIYKKLY HSDACSSKAV VSLRCIACGV NLNDDDDDKI VGGESALPGA W PWQVSLHV QNVHVCGGSI ITPEWIVTAA HCVEKPLNNP WHWTAFAGIL RQSFMFYGAG YQVEKVISHP NYDSKTKNND IA LMKLQKP LTFNDLVKPV CLPNPGMMLQ PEQLCWISGW GATEEKGKTS EVLNAAKVLL IETQRCNSRY VYDNLITPAM ICA GFLQGN VDSCQGDSGG PLVTSKNNIW WLIGDTSWGS GCAKAYRPGV YGNVMVFTDW IYRQMRADGE NLYFQ

UniProtKB: Transmembrane protease serine 2

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Macromolecule #2: Fab 752 light chain

MacromoleculeName: Fab 752 light chain / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Mus musculus (house mouse)
Molecular weightTheoretical: 23.749342 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: DIQMTQSPSS LSASLGGKVT ITCKASQDIN KYIAWYQHKP GKGPRLLIHY TSTLQPGIPS RFSGSGSGRD YSFSIYNLEP EDIATYYCL QYYNLWTFGG GTKLEIKRAD AAPTVSIFPP SSEQLTSGGA SVVCFLNNFY PKDINVKWKI DGSERQNGVL N SWTDQDSK ...String:
DIQMTQSPSS LSASLGGKVT ITCKASQDIN KYIAWYQHKP GKGPRLLIHY TSTLQPGIPS RFSGSGSGRD YSFSIYNLEP EDIATYYCL QYYNLWTFGG GTKLEIKRAD AAPTVSIFPP SSEQLTSGGA SVVCFLNNFY PKDINVKWKI DGSERQNGVL N SWTDQDSK DSTYSMSSTL TLTKDEYERH NSYTCEATHK TSTSPIVKSF NRNEC

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Macromolecule #3: Fab 752 heavy chain

MacromoleculeName: Fab 752 heavy chain / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Mus musculus (house mouse)
Molecular weightTheoretical: 24.654529 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: DQVQLQQSGA ELARPGASVK LSCKASGYTF TSCGISWVKQ RTGQGLEWIG EIYPRGGNTY YNEKFKGKAT LTADKSSSTA YMELRSLTS EDSAVYFCAR ENGNYDPLFA YWGQGTLVTV SAAKTTPPSV YPLAPGSAAQ TNSMVTLGCL VKGYFPEPVT V TWNSGSLS ...String:
DQVQLQQSGA ELARPGASVK LSCKASGYTF TSCGISWVKQ RTGQGLEWIG EIYPRGGNTY YNEKFKGKAT LTADKSSSTA YMELRSLTS EDSAVYFCAR ENGNYDPLFA YWGQGTLVTV SAAKTTPPSV YPLAPGSAAQ TNSMVTLGCL VKGYFPEPVT V TWNSGSLS SGVHTFPAVL QSDLYTLSSS VTVPSSTWPS QTVTCNVAHP ASSTKVDKKI VPRDCENLYF Q

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Macromolecule #4: Fab 2228 light chain

MacromoleculeName: Fab 2228 light chain / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Mus musculus (house mouse)
Molecular weightTheoretical: 23.919504 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: DVVVTQSPAS LAVSLGQRAT ISCRASKSVS TSGYSFMHWY QQKPGQPPKL LIYLASNLES GVPARFSGSG SGTDFILNIH PVEEEDAAT YYCQHSRELP LTFGAGTKLE LKRADAAPTV SIFPPSSEQL TSGGASVVCF LNNFYPKDIN VKWKIDGSER Q NGVLNSWT ...String:
DVVVTQSPAS LAVSLGQRAT ISCRASKSVS TSGYSFMHWY QQKPGQPPKL LIYLASNLES GVPARFSGSG SGTDFILNIH PVEEEDAAT YYCQHSRELP LTFGAGTKLE LKRADAAPTV SIFPPSSEQL TSGGASVVCF LNNFYPKDIN VKWKIDGSER Q NGVLNSWT DQDSKDSTYS MSSTLTLTKD EYERHNSYTC EATHKTSTSP IVKSFNRNEC

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Macromolecule #5: Fab 2228 heavy chain

MacromoleculeName: Fab 2228 heavy chain / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Mus musculus (house mouse)
Molecular weightTheoretical: 24.584455 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: DQVQLQQSGP ELVKPGTSVK ISCKASGYTF TDYYINWVKQ RPGQGLEWIG WIFPGSGSSY YNAIFKGKAT LTVDTSSNTA HMSLSSLTS DDSAVYFCAR GDFGNFGGFF TYWGQGTLVT VSAAKTTAPS VYPLAPVCGG TTGSSVTLGC LVKGYFPEPV T LTWNSGSL ...String:
DQVQLQQSGP ELVKPGTSVK ISCKASGYTF TDYYINWVKQ RPGQGLEWIG WIFPGSGSSY YNAIFKGKAT LTVDTSSNTA HMSLSSLTS DDSAVYFCAR GDFGNFGGFF TYWGQGTLVT VSAAKTTAPS VYPLAPVCGG TTGSSVTLGC LVKGYFPEPV T LTWNSGSL SSGVHTFPAL LQSGLYTLSS SVTVTSNTWP SQTITCNVAH PASSTKVDKK IEPRVPENLY FQ

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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

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Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K3 BIOCONTINUUM (6k x 4k) / Average electron dose: 50.1 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 20.0 µm / Nominal defocus min: 8.0 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

CTF correctionDetails: CTFFind4 and CTFRefine were used within the RELION3.1.3
Type: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: NONE / Details: Initial model generation in cryoSPARC.
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.15 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 80052
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

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