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- EMDB-37462: CryoEM structure of the spike protein of human CoV 229E in comple... -

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Basic information

Entry
Database: EMDB / ID: EMD-37462
TitleCryoEM structure of the spike protein of human CoV 229E in complex with receptor hAPN (composite map)
Map data
Sample
  • Complex: CryoEM structure of the spike protein of human CoV 229E in complex with receptor hAPN (composite map)
    • Protein or peptide: Spike glycoprotein
    • Protein or peptide: Aminopeptidase N
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
Keywordshuman aminopeptidase N / VIRAL PROTEIN
Function / homology
Function and homology information


alanyl aminopeptidase activity / membrane alanyl aminopeptidase / peptide catabolic process / endoplasmic reticulum-Golgi intermediate compartment / metalloaminopeptidase activity / aminopeptidase activity / Metabolism of Angiotensinogen to Angiotensins / angiotensin maturation / peptide binding / secretory granule membrane ...alanyl aminopeptidase activity / membrane alanyl aminopeptidase / peptide catabolic process / endoplasmic reticulum-Golgi intermediate compartment / metalloaminopeptidase activity / aminopeptidase activity / Metabolism of Angiotensinogen to Angiotensins / angiotensin maturation / peptide binding / secretory granule membrane / metallopeptidase activity / signaling receptor activity / virus receptor activity / angiogenesis / cell differentiation / external side of plasma membrane / lysosomal membrane / Neutrophil degranulation / proteolysis / extracellular space / extracellular exosome / zinc ion binding / plasma membrane / cytoplasm
Similarity search - Function
Aminopeptidase N-type / ERAP1-like C-terminal domain / : / ERAP1-like C-terminal domain / Peptidase M1, alanine aminopeptidase/leukotriene A4 hydrolase / Peptidase M1, membrane alanine aminopeptidase / Aminopeptidase N-like , N-terminal domain / Peptidase family M1 domain / Peptidase M1 N-terminal domain / Aminopeptidase N-like , N-terminal domain superfamliy ...Aminopeptidase N-type / ERAP1-like C-terminal domain / : / ERAP1-like C-terminal domain / Peptidase M1, alanine aminopeptidase/leukotriene A4 hydrolase / Peptidase M1, membrane alanine aminopeptidase / Aminopeptidase N-like , N-terminal domain / Peptidase family M1 domain / Peptidase M1 N-terminal domain / Aminopeptidase N-like , N-terminal domain superfamliy / Peptidase M4/M1, CTD superfamily / Neutral zinc metallopeptidases, zinc-binding region signature.
Similarity search - Domain/homology
Biological speciesHuman coronavirus 229E / Homo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.6 Å
AuthorsHsu STD / Tsai YX
Funding support Taiwan, 9 items
OrganizationGrant numberCountry
Academia Sinica (Taiwan)AS-CDA-109-L08 Taiwan
Academia Sinica (Taiwan)AS-IDR-112-04 Taiwan
Academia Sinica (Taiwan)AS-IDR-111-03 Taiwan
National Science Council (NSC, Taiwan)110-2113-M-001-050-MY3 Taiwan
National Science Council (NSC, Taiwan)110-2311-B-001-013-MY3 Taiwan
Academia Sinica (Taiwan)AS-CFII-111-201 Taiwan
Academia Sinica (Taiwan)AS-CFII-111-209 Taiwan
Academia Sinica (Taiwan)AS-CFII-111-210 Taiwan
Academia Sinica (Taiwan)AS-KPQ-109-TPP2 Taiwan
CitationJournal: Nat Commun / Year: 2025
Title: Molecular basis of host recognition of human coronavirus 229E.
Authors: Yu-Xi Tsai / Yu-Chun Chien / Min-Feng Hsu / Kay-Hooi Khoo / Shang-Te Danny Hsu /
Abstract: Human coronavirus 229E (HCoV-229E) is the earliest CoV found to infect humans. It binds to the human aminopeptidase N (hAPN) through the receptor binding domain (RBD) of its spike (S) protein to ...Human coronavirus 229E (HCoV-229E) is the earliest CoV found to infect humans. It binds to the human aminopeptidase N (hAPN) through the receptor binding domain (RBD) of its spike (S) protein to achieve host recognition. We present the cryo-electron microscopy structure of two HCoV-229E S protein in complex with a dimeric hAPN to provide structural insights on how the HCoV-229E S protein opens up its RBD to engage with its host receptor, information that is currently missing among alphacoronaviruses to which HCoV-229E belong. We quantitatively profile the glycosylation of HCoV-229E S protein and hAPN to deduce the glyco-shielding effects pertinent to antigenicity and host recognition. Finally, we present an atomic model of fully glycosylated HCoV-229E S in complex with hAPN anchored on their respective membrane bilayers to recapitulate the structural basis of the first step of host infection by HCoV-229E.
History
DepositionSep 15, 2023-
Header (metadata) releaseMar 5, 2025-
Map releaseMar 5, 2025-
UpdateMar 12, 2025-
Current statusMar 12, 2025Processing site: PDBj / Status: Released

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Structure visualization

Supplemental images

Downloads & links

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Map

FileDownload / File: emd_37462.map.gz / Format: CCP4 / Size: 824 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesX (Sec.)Y (Row.)Z (Col.)
1.48 Å/pix.
x 600 pix.
= 885.6 Å
1.48 Å/pix.
x 600 pix.
= 885.6 Å
1.48 Å/pix.
x 600 pix.
= 885.6 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.476 Å
Density
Contour LevelBy AUTHOR: 18.0
Minimum - Maximum-34.766579999999998 - 83.062706000000006
Average (Standard dev.)-0.0141009 (±0.8528265)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderZYX
Origin000
Dimensions600600600
Spacing600600600
CellA=B=C: 885.60004 Å
α=β=γ: 90.0 °

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Supplemental data

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Sample components

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Entire : CryoEM structure of the spike protein of human CoV 229E in comple...

EntireName: CryoEM structure of the spike protein of human CoV 229E in complex with receptor hAPN (composite map)
Components
  • Complex: CryoEM structure of the spike protein of human CoV 229E in complex with receptor hAPN (composite map)
    • Protein or peptide: Spike glycoprotein
    • Protein or peptide: Aminopeptidase N
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose

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Supramolecule #1: CryoEM structure of the spike protein of human CoV 229E in comple...

SupramoleculeName: CryoEM structure of the spike protein of human CoV 229E in complex with receptor hAPN (composite map)
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2
Source (natural)Organism: Human coronavirus 229E

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Macromolecule #1: Spike glycoprotein

MacromoleculeName: Spike glycoprotein / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Human coronavirus 229E
Molecular weightTheoretical: 127.915492 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: GTQTTNGLNT SYSVCNGCVG YSENVFAVES GGYIPSDFAF NNWFLLTNTS SVVDGVVRSF QPLLLNCLWS VSGLRFTTGF VYFNGTGRG DCKGFSSDVL SDVIRYNLNF EENLRRGTIL FKTSYGVVVF YCTNNTLVSG DAHIPFGTVL GNFYCFVNTT I GTETTSAF ...String:
GTQTTNGLNT SYSVCNGCVG YSENVFAVES GGYIPSDFAF NNWFLLTNTS SVVDGVVRSF QPLLLNCLWS VSGLRFTTGF VYFNGTGRG DCKGFSSDVL SDVIRYNLNF EENLRRGTIL FKTSYGVVVF YCTNNTLVSG DAHIPFGTVL GNFYCFVNTT I GTETTSAF VGALPKTVRE FVISRTGHFY INGYRYFTLG NVEAVNFNVT TAETTDFFTV ALASYADVLV NVSQTSIANI IY CNSVINR LRCDQLSFYV PDGFYSTSPI QSVELPVSIV SLPVYHKHMF IVLYVDFKPQ SGGGKCFNCY PAGVNITLAN FNE TKGPLC VDTSHFTTKY VAVYANVGRW SASINTGNCP FSFGKVNNFV KFGSVCFSLK DIPGGCAMPI VANWAYSKYY TIGT LYVSW SDGDGITGVP QPVEGVSSFM NVTLDKCTKY NIYDVSGVGV IRVSNDTFLN GITYTSTSGN LLGFKDVTKG TIYSI TPCN PPDQLVVYQQ AVVGAMLSEN FTSYGFSNVV ELPKFFYASN GTYNCTDAVL TYSSFGVCAD GSIIAVQPRN VSYDSV SAI VTANLSIPSN WTISVQVEYL QITSTPIVVD CSTYVCNGNV RCVELLKQYT SACKTIEDAL RNSARLESAD VSEMLTF DK KAFTLANVSS FGDYNLSSVI PSLPTSGSRV AGRSAIEDIL FSKIVTSGLG TVDADYKNCT KGLSIADLAC AQYYNGIM V LPGVADAERM AMYTGSLIGG IALGGLTSAV SIPFSLAIQA RLNYVALQTD VLQENQKILA ASFNKAMTNI VDAFTGVND AITQTSQALQ TVATALNKIQ DVVNQQGNSL NHLTSQLRQN FQAISSSIQA IYDRLDPPQA DQQVDRLITG RLAALNVFVS HTLTKYTEV RASRQLAQQK VNECVKSQSK RYGFCGNGTH IFSIVNAAPE GLVFLHTVLL PTQYKDVEAW SGLCVDGTNG Y VLRQPNLA LYKEGNYYRI TSRIMFEPRI PTMADFVQIE NCNVTFVNIS RSELQTIVPE YIDVNKTLQE LSYKLPNYTV PD LVVEQYN QTILNLTSEI STLENKSAEL NYTVQKLQTL IDNINSTLVD LKWLNRVETY IKGSGRENLY FQGGGGSGYI PEA PRDGQA YVRKDGEWVL LSTFLGHHHH HHHHGLNDIF EAQKIEWHE

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Macromolecule #2: Aminopeptidase N

MacromoleculeName: Aminopeptidase N / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 107.906734 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: DQSKAWNRYR LPNTLKPDSY RVTLRPYLTP NDRGLYVFKG SSTVRFTCKE ATDVIIIHSK KLNYTLSQGH RVVLRGVGGS QPPDIDKTE LVEPTEYLVV HLKGSLVKDS QYEMDSEFEG ELADDLAGFY RSEYMEGNVR KVVATTQMQA ADARKSFPCF D EPAMKAEF ...String:
DQSKAWNRYR LPNTLKPDSY RVTLRPYLTP NDRGLYVFKG SSTVRFTCKE ATDVIIIHSK KLNYTLSQGH RVVLRGVGGS QPPDIDKTE LVEPTEYLVV HLKGSLVKDS QYEMDSEFEG ELADDLAGFY RSEYMEGNVR KVVATTQMQA ADARKSFPCF D EPAMKAEF NITLIHPKDL TALSNMLPKG PSTPLPEDPN WNVTEFHTTP KMSTYLLAFI VSEFDYVEKQ ASNGVLIRIW AR PSAIAAG HGDYALNVTG PILNFFAGHY DTPYPLPKSD QIGLPDFNAG AMENWGLVTY RENSLLFDPL SSSSSNKERV VTV IAHELA HQWFGNLVTI EWWNDLWLNE GFASYVEYLG ADYAEPTWNL KDLMVLNDVY RVMAVDALAS SHPLSTPASE INTP AQISE LFDAISYSKG ASVLRMLSSF LSEDVFKQGL ASYLHTFAYQ NTIYLNLWDH LQEAVNNRSI QLPTTVRDIM NRWTL QMGF PVITVDTSTG TLSQEHFLLD PDSNVTRPSE FNYVWIVPIT SIRDGRQQQD YWLIDVRAQN DLFSTSGNEW VLLNLN VTG YYRVNYDEEN WRKIQTQLQR DHSAIPVINR AQIINDAFNL ASAHKVPVTL ALNNTLFLIE ERQYMPWEAA LSSLSYF KL MFDRSEVYGP MKNYLKKQVT PLFIHFRNNT NNWREIPENL MDQYSEVNAI STACSNGVPE CEEMVSGLFK QWMENPNN N PIHPNLRSTV YCNAIAQGGE EEWDFAWEQF RNATLVNEAD KLRAALACSK ELWILNRYLS YTLNPDLIRK QDATSTIIS ITNNVIGQGL VWDFVQSNWK KLFNDYGGGS FSFSNLIQAV TRRFSTEYEL QQLEQFKKDN EETGFGSGTR ALEQALEKTK ANIKWVKEN KEVVLQWFTE NSKQDNSADI QHSGRPLESR GPFEQKLISE EDLNMHTGHH HHHH

UniProtKB: Aminopeptidase N

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Macromolecule #5: 2-acetamido-2-deoxy-beta-D-glucopyranose

MacromoleculeName: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 5 / Number of copies: 20 / Formula: NAG
Molecular weightTheoretical: 221.208 Da
Chemical component information

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

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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: 7.6
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TITAN 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: 3.0 µm / Nominal defocus min: 1.0 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Startup modelType of model: PDB ENTRY
PDB model - PDB ID:
Final reconstructionApplied symmetry - Point group: C1 (asymmetric) / Resolution.type: BY AUTHOR / Resolution: 3.6 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 253164
Initial angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC (ver. 4.1.1)
Final angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC (ver. 4.1.1)

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