[English] 日本語
Yorodumi
- EMDB-73786: HCoV-NL63 S2' peptide bound to TMPRSS2 S441A (complexed with the ... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-73786
TitleHCoV-NL63 S2' peptide bound to TMPRSS2 S441A (complexed with the H1H7 Fab and an anti-kappa-nanobody)
Map datasharpened map
Sample
  • Complex: HCoV-NL63 S2' peptide bound to TMPRSS2 S441A (complexed with the H1H7 Fab and an anti-kappa-nanobody)
    • Protein or peptide: HCoV-NL63 S2' peptide
    • Protein or peptide: Inactive TMPRSS2 construct
    • Protein or peptide: H1H7 heavy chain
    • Protein or peptide: H1H7 light chain
    • Protein or peptide: anti-kappa nanobody
  • Ligand: water
KeywordsTMPRSS2 / NL63 / S2prime / coronavirus / cleavage / SARS-CoV-2 / spike / fusion / protease / entry / antiviral / Structural Genomics / Seattle Structural Genomics Center for Infectious Disease / SSGCID / VIRAL PROTEIN / VIRAL PROTEIN-Immune System complex
Function / homology
Function and homology information


transmembrane protease serine 2 / protein autoprocessing / Attachment and Entry / serine-type peptidase activity / Induction of Cell-Cell Fusion / positive regulation of viral entry into host cell / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / Attachment and Entry / entry receptor-mediated virion attachment to host cell / receptor-mediated virion attachment to host cell ...transmembrane protease serine 2 / protein autoprocessing / Attachment and Entry / serine-type peptidase activity / Induction of Cell-Cell Fusion / positive regulation of viral entry into host cell / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / Attachment and Entry / entry receptor-mediated virion attachment to host cell / receptor-mediated virion attachment to host cell / host cell surface receptor binding / endocytosis involved in viral entry into host cell / fusion of virus membrane with host plasma membrane / serine-type endopeptidase activity / fusion of virus membrane with host endosome membrane / viral envelope / virion membrane / proteolysis / extracellular exosome / extracellular region / nucleoplasm / membrane / plasma membrane
Similarity search - Function
Spike glycoprotein, Alphacoronavirus / Scavenger receptor cysteine-rich domain / Spike glycoprotein S1, coronavirus / Coronavirus spike glycoprotein S1 / SRCR domain profile. / SRCR-like domain superfamily / Scavenger receptor Cys-rich / SRCR domain / Spike glycoprotein S2, coronavirus, C-terminal / Coronavirus spike glycoprotein S2, intravirion ...Spike glycoprotein, Alphacoronavirus / Scavenger receptor cysteine-rich domain / Spike glycoprotein S1, coronavirus / Coronavirus spike glycoprotein S1 / SRCR domain profile. / SRCR-like domain superfamily / Scavenger receptor Cys-rich / SRCR domain / Spike glycoprotein S2, coronavirus, C-terminal / Coronavirus spike glycoprotein S2, intravirion / 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 / Coronavirus spike glycoprotein S1, C-terminal / Coronavirus spike glycoprotein S1, C-terminal / Spike glycoprotein S2 superfamily, coronavirus / Spike glycoprotein S2, coronavirus, heptad repeat 1 / Spike glycoprotein S2, coronavirus, heptad repeat 2 / Coronavirus spike (S) glycoprotein S2 subunit heptad repeat 1 (HR1) region profile. / Coronavirus spike (S) glycoprotein S2 subunit heptad repeat 2 (HR2) region profile. / Spike glycoprotein S2, coronavirus / Coronavirus spike glycoprotein S2 / Peptidase S1, PA clan, chymotrypsin-like fold / Peptidase S1, PA clan
Similarity search - Domain/homology
Transmembrane protease serine 2 / Spike glycoprotein
Similarity search - Component
Biological speciesHomo sapiens (human) / Human coronavirus NL63 / Lama glama (llama)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.8 Å
AuthorsMcCallum M / Seattle Structural Genomics Center for Infectious Disease (SSGCID) / Veesler D
Funding support United States, 1 items
OrganizationGrant numberCountry
Howard Hughes Medical Institute (HHMI) United States
CitationJournal: Nat Struct Mol Biol / Year: 2026
Title: TMPRSS2-mediated coronavirus spike activation and inhibition.
Authors: Matthew McCallum / James Brett Case / Jack T Brown / Young-Jun Park / Jimin Lee / Emmajay Sutherland / Anupriya Aggarwal / Cecily Gibson / Florian A Lempp / Cameron Stewart / M Alejandra ...Authors: Matthew McCallum / James Brett Case / Jack T Brown / Young-Jun Park / Jimin Lee / Emmajay Sutherland / Anupriya Aggarwal / Cecily Gibson / Florian A Lempp / Cameron Stewart / M Alejandra Tortorici / Shilpa Sanapala / Jun Siong Low / Daniel Asarnow / Dana Bohan / Exequiel Dellota / Benjamin Merz / Bhavna Chawla / Swagata Kar / Antonio Lanzavecchia / Federica Sallusto / Nicholas M Riley / Stuart Turville / Lisa Purcell / Michael S Diamond / David Veesler /
Abstract: The protease TMPRSS2 facilitates coronavirus infections, yet its mechanism of viral glycoprotein recognition remains unclear. Here we show that, following ACE2 engagement of the SARS-CoV-2 spike (S) ...The protease TMPRSS2 facilitates coronavirus infections, yet its mechanism of viral glycoprotein recognition remains unclear. Here we show that, following ACE2 engagement of the SARS-CoV-2 spike (S) inducing the early fusion intermediate conformation (E-FIC), TMPRSS2 cleaves the R815 S' site and promotes fusogenic conformational changes leading to viral entry. We unveil TMPRSS2 recognition of S', identify key residues modulating binding specificity and demonstrate that S' site-directed broadly neutralizing antibodies target E-FIC and inhibit viral entry by blocking TMPRSS2 access. We computationally designed stabilized E-FIC as a vaccine candidate, overcoming the transient nature of this state. We describe a TMPRSS2-directed monoclonal antibody inhibiting several coronaviruses, including SARS-CoV-2 variants and protecting mice against SARS-CoV-2 challenge. These results outline the mechanistic role of TMPRSS2 and S' site-directed antibodies in coronavirus entry.
History
DepositionNov 6, 2025-
Header (metadata) releaseMay 13, 2026-
Map releaseMay 13, 2026-
UpdateMay 13, 2026-
Current statusMay 13, 2026Processing site: RCSB / Status: Released

-
Structure visualization

Supplemental images

emd_73786.png

Downloads & links

-
Map

FileDownload / File: emd_73786.map.gz / Format: CCP4 / Size: 512 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Annotationsharpened map
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.83 Å/pix.
x 512 pix.
= 424.448 Å		0.83 Å/pix.
x 512 pix.
= 424.448 Å		0.83 Å/pix.
x 512 pix.
= 424.448 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.829 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.64
Minimum - Maximum-4.5752306 - 6.339953
Average (Standard dev.)0.00016775905 (±0.06897751)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions512512512
Spacing512512512
CellA=B=C: 424.448 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Additional map: unsharpened map

Fileemd_73786_additional_1.map
Annotationunsharpened map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: half map A

Fileemd_73786_half_map_1.map
Annotationhalf map A
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: half map B

Fileemd_73786_half_map_2.map
Annotationhalf map B
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : HCoV-NL63 S2' peptide bound to TMPRSS2 S441A (complexed with the ...

EntireName: HCoV-NL63 S2' peptide bound to TMPRSS2 S441A (complexed with the H1H7 Fab and an anti-kappa-nanobody)
Components
  • Complex: HCoV-NL63 S2' peptide bound to TMPRSS2 S441A (complexed with the H1H7 Fab and an anti-kappa-nanobody)
    • Protein or peptide: HCoV-NL63 S2' peptide
    • Protein or peptide: Inactive TMPRSS2 construct
    • Protein or peptide: H1H7 heavy chain
    • Protein or peptide: H1H7 light chain
    • Protein or peptide: anti-kappa nanobody
  • Ligand: water

-
Supramolecule #1: HCoV-NL63 S2' peptide bound to TMPRSS2 S441A (complexed with the ...

SupramoleculeName: HCoV-NL63 S2' peptide bound to TMPRSS2 S441A (complexed with the H1H7 Fab and an anti-kappa-nanobody)
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#5
Source (natural)Organism: Homo sapiens (human)

-
Macromolecule #1: HCoV-NL63 S2' peptide

MacromoleculeName: HCoV-NL63 S2' peptide / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Human coronavirus NL63
Molecular weightTheoretical: 1.678952 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
RIAGRSALED LLFSK

UniProtKB: Spike glycoprotein

-
Macromolecule #2: Inactive TMPRSS2 construct

MacromoleculeName: Inactive TMPRSS2 construct / type: protein_or_peptide / ID: 2
Details: The inactive TMPRSS2 construct comprises an azurocidin signal peptide (MTRLTVLALLAGLLASSRA), a serine residue, a SUMO tag (UniProt Q12306; 1-94, ...Details: The inactive TMPRSS2 construct comprises an azurocidin signal peptide (MTRLTVLALLAGLLASSRA), a serine residue, a SUMO tag (UniProt Q12306; 1-94, MSDSEVNQEAKPEVKPEVKPETHINLKVSDGSSEIFFKIKKTTPLRRLMEAFAKRQGKEMDSLRFLYDGIRIQADQTPEDLDMEDNDIIEAHREN), an enteropeptidase cleavage site (NDDDDK), a TT linker, residues 109-492 of TMPRSS2 (UniProt O15393; numbering without start methionine), a C-terminal enteropeptidase site (DDDDK), an SG linker and an octahistidine tag. TMPRSS2 harbors the following substitutions: an internal enteropeptidase site introduced by substituting R251QSR254 to DDDDK, the S441A substitution to make it catalytically inactive and the T447C stabilizing substitution
Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 57.81682 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MTRLTVLALL AGLLASSRAS MSDSEVNQEA KPEVKPEVKP ETHINLKVSD GSSEIFFKIK KTTPLRRLME AFAKRQGKEM DSLRFLYDG IRIQADQTPE DLDMEDNDII EAHRENDDDD KTTGSKCSNS GIECDSSGTC INPSNWCDGV SHCPGGEDEN R CVRLYGPN ...String:
MTRLTVLALL AGLLASSRAS MSDSEVNQEA KPEVKPEVKP ETHINLKVSD GSSEIFFKIK KTTPLRRLME AFAKRQGKEM DSLRFLYDG IRIQADQTPE DLDMEDNDII EAHRENDDDD KTTGSKCSNS GIECDSSGTC INPSNWCDGV SHCPGGEDEN R CVRLYGPN FILQVYSSQR KSWHPVCQDD WNENYGRAAC RDMGYKNNFY SSQGIVDDSG STSFMKLNTS AGNVDIYKKL YH SDACSSK AVVSLRCIAC GVNLNDDDDK IVGGESALPG AWPWQVSLHV QNVHVCGGSI ITPEWIVTAA HCVEKPLNNP WHW TAFAGI LRQSFMFYGA GYQVEKVISH PNYDSKTKNN DIALMKLQKP LTFNDLVKPV CLPNPGMMLQ PEQLCWISGW GATE EKGKT SEVLNAAKVL LIETQRCNSR YVYDNLITPA MICAGFLQGN VDSCQGDAGG PLVCSKNNIW WLIGDTSWGS GCAKA YRPG VYGNVMVFTD WIYRQMRADG DDDDKSGHHH HHHHH

UniProtKB: Transmembrane protease serine 2, Transmembrane protease serine 2

-
Macromolecule #3: H1H7 heavy chain

MacromoleculeName: H1H7 heavy chain / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 24.054004 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: QVQLVESGGG VVQPGRSLRL SCAASGFTFS SYGMHWVRQS PGKGLEWVAV IWNDGSYVYY ADSVKGRFTI SRDISKNTLF LQMNSLRAE DTAVYYCARE GEWVLYYFDY WGQGTLVTVS SASTKGPSVF PLAPSSKSTS GGTAALGCLV KDYFPEPVTV S WNSGALTS ...String:
QVQLVESGGG VVQPGRSLRL SCAASGFTFS SYGMHWVRQS PGKGLEWVAV IWNDGSYVYY ADSVKGRFTI SRDISKNTLF LQMNSLRAE DTAVYYCARE GEWVLYYFDY WGQGTLVTVS SASTKGPSVF PLAPSSKSTS GGTAALGCLV KDYFPEPVTV S WNSGALTS GVHTFPAVLQ SSGLYSLSSV VTVPSSSLGT QTYICNVNHK PSNTKVDKKV EPKSC

-
Macromolecule #4: H1H7 light chain

MacromoleculeName: H1H7 light chain / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 23.510062 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: DIQMTQSPST LSASVGDRVT ITCRASQSIS SWLAWYQQKP GKAPKLLIYK ASTLESGVPS RFSGSGSGTE FTLTISSLQP DDFATYYCQ QYNSYSYTFG QGTKLEIKRT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF YPREAKVQWK VDNALQSGNS Q ESVTEQDS ...String:
DIQMTQSPST LSASVGDRVT ITCRASQSIS SWLAWYQQKP GKAPKLLIYK ASTLESGVPS RFSGSGSGTE FTLTISSLQP DDFATYYCQ QYNSYSYTFG QGTKLEIKRT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF YPREAKVQWK VDNALQSGNS Q ESVTEQDS KDSTYSLSST LTLSKADYEK HKVYACEVTH QGLSSPVTKS FNRGEC

-
Macromolecule #5: anti-kappa nanobody

MacromoleculeName: anti-kappa nanobody / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Lama glama (llama)
Molecular weightTheoretical: 17.252107 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString:
MKKTAIAIAV ALAGFATVAQ AAPMGSQVQL QESGGGLVQP GGSLRLSCAA SGRTISRYAM SWFRQAPGKE REFVAVARRS GDGAFYADS VQGRFTVSRD DAKNTVYLQM NSLKPEDTAV YYCAIDSDTF YSGSYDYWGQ GTQVTVSSHH HHHHHHEPEA

-
Macromolecule #7: water

MacromoleculeName: water / type: ligand / ID: 7 / Number of copies: 89 / Formula: HOH
Molecular weightTheoretical: 18.015 Da
Chemical component information

ChemComp-HOH:
WATER

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

BufferpH: 7.5
VitrificationCryogen name: ETHANE

-
Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K3 (6k 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: 2.7 µm / Nominal defocus min: 0.2 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

+
Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: INSILICO MODEL
Final reconstructionResolution.type: BY AUTHOR / Resolution: 2.8 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 270089
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD

+
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