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- EMDB-71242: Structure of ANDV dimer of tetramer at conformation III -

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Basic information

Entry
Database: EMDB / ID: EMD-71242
TitleStructure of ANDV dimer of tetramer at conformation III
Map data
Sample
  • Complex: Dimer of ANDV GN-Gc heterotetramer
    • Protein or peptide: Glycoprotein N
    • Protein or peptide: Glycoprotein C
KeywordsANDV / hantavirus glycoprotein / dimer of tetramer / Gn and Gc / VIRAL PROTEIN
Function / homology
Function and homology information


symbiont-mediated suppression of host TRAF-mediated signal transduction / host cell Golgi membrane / host cell mitochondrion / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity / host cell surface / host cell endoplasmic reticulum membrane / endocytosis involved in viral entry into host cell / symbiont-mediated activation of host autophagy / fusion of virus membrane with host endosome membrane / viral envelope ...symbiont-mediated suppression of host TRAF-mediated signal transduction / host cell Golgi membrane / host cell mitochondrion / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity / host cell surface / host cell endoplasmic reticulum membrane / endocytosis involved in viral entry into host cell / symbiont-mediated activation of host autophagy / fusion of virus membrane with host endosome membrane / viral envelope / virion attachment to host cell / virion membrane / signal transduction / zinc ion binding / membrane
Similarity search - Function
Hantavirus glycoprotein Gn / ITAM motif, hantavirus type / Envelope glycoprotein precursor, Hantavirus / : / Hantavirus glycoprotein Gn, head / Hantavirus ITAM motif / Hantavirus glycoprotein Gn, base / ITAM motif hantavirus type profile. / Hantavirus glycoprotein Gc / : ...Hantavirus glycoprotein Gn / ITAM motif, hantavirus type / Envelope glycoprotein precursor, Hantavirus / : / Hantavirus glycoprotein Gn, head / Hantavirus ITAM motif / Hantavirus glycoprotein Gn, base / ITAM motif hantavirus type profile. / Hantavirus glycoprotein Gc / : / Hantavirus glycoprotein Gc, N-terminal / Hantavirus glycoprotein Gc, C-terminal
Similarity search - Domain/homology
Envelopment polyprotein
Similarity search - Component
Biological speciesOrthohantavirus andesense
Methodsingle particle reconstruction / cryo EM / Resolution: 3.37 Å
AuthorsLuqiang G / McLellan JS
Funding support United States, 1 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID) United States
CitationJournal: bioRxiv / Year: 2025
Title: High-resolution in situ structures of hantavirus glycoprotein tetramers.
Abstract: New World hantaviruses cause severe infections in humans, with case fatality rates approaching 40%. Previous structural studies have advanced our understanding of hantavirus glycoprotein architecture ...New World hantaviruses cause severe infections in humans, with case fatality rates approaching 40%. Previous structural studies have advanced our understanding of hantavirus glycoprotein architecture and function, however, the lack of high-resolution in situ structures of the glycoprotein tetramer and its lattice organization has limited mechanistic insights into viral assembly, entry, and antigenicity. Here, we leveraged a virus-like particle (VLP) system to establish a cryo-electron microscopy workflow for lattice-forming viral glycoproteins. This enabled the determination of a 2.35 Å resolution structure of the membrane-embedded Andes virus (ANDV) glycoprotein tetramer, as well as structures of dimers of tetramers and a complex with antibody ADI-65534. These structures reveal previously uncharacterized features of glycoprotein organization, stability, and pH-sensing. Immunization of mice with self-amplifying replicon RNA (repRNA) encoding ANDV-VLPs elicited high levels of glycoprotein-binding antibodies but equivalent titers of neutralizing antibodies compared to repRNA-encoded native ANDV glycoprotein complex. Collectively, these findings advance our understanding of hantavirus glycoprotein assemblies and their function, laying a foundation for structure-based vaccine design efforts.
History
DepositionJun 14, 2025-
Header (metadata) releaseJul 30, 2025-
Map releaseJul 30, 2025-
UpdateJul 30, 2025-
Current statusJul 30, 2025Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

Downloads & links

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Map

FileDownload / File: emd_71242.map.gz / Format: CCP4 / Size: 600.7 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.83 Å/pix.
x 540 pix.
= 449.28 Å
0.83 Å/pix.
x 540 pix.
= 449.28 Å
0.83 Å/pix.
x 540 pix.
= 449.28 Å

Surface

Projections

Slices (1/3)

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Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.832 Å
Density
Contour LevelBy AUTHOR: 0.02
Minimum - Maximum-0.064750895 - 0.13615295
Average (Standard dev.)0.0005957538 (±0.00583971)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions540540540
Spacing540540540
CellA=B=C: 449.28 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #2

Fileemd_71242_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Half map: #1

Fileemd_71242_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Sample components

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Entire : Dimer of ANDV GN-Gc heterotetramer

EntireName: Dimer of ANDV GN-Gc heterotetramer
Components
  • Complex: Dimer of ANDV GN-Gc heterotetramer
    • Protein or peptide: Glycoprotein N
    • Protein or peptide: Glycoprotein C

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Supramolecule #1: Dimer of ANDV GN-Gc heterotetramer

SupramoleculeName: Dimer of ANDV GN-Gc heterotetramer / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Orthohantavirus andesense

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Macromolecule #1: Glycoprotein N

MacromoleculeName: Glycoprotein N / type: protein_or_peptide / ID: 1 / Number of copies: 8 / Enantiomer: LEVO
Source (natural)Organism: Orthohantavirus andesense
Molecular weightTheoretical: 72.162602 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MEGWYLVVLG VCYTLTLAMP KTIYELKMEC PHTVGLGQGY IIGSTELGLI SIEAASDIKL ESSCNFDLHT TSMAQKSFTQ VEWRKKSDT TDTTNAASTT FEAQTKTVNL RGTCILAPEL YDTLKKVKKT VLCYDLTCNQ THCQPTVYLI APVLTCMSIR S CMASVFTS ...String:
MEGWYLVVLG VCYTLTLAMP KTIYELKMEC PHTVGLGQGY IIGSTELGLI SIEAASDIKL ESSCNFDLHT TSMAQKSFTQ VEWRKKSDT TDTTNAASTT FEAQTKTVNL RGTCILAPEL YDTLKKVKKT VLCYDLTCNQ THCQPTVYLI APVLTCMSIR S CMASVFTS RIQVIYEKTH CVTGQLIEGQ CFNPAHTLTL SQPAHTYDTV TLPISCFFTP KKSEQLKVIK TFEGILTKTG CT ENALQGY YVCFLGSHSE PLIVPSLEDI RSAEVVSRML VHPRGEDHDA IQNSQSHLRI VGPITAKVPS TSSTDTLKGT AFA GVPMYS SLSTLVRNAD PEFVFSPGIV PESNHSTCDK KTVPITWTGY LPISGEMEKV TGCTVFCTLA GPGASCEAYS ENGI FNISS PTCLVNKVQR FRGSEQKINF ICQRVDQDVV VYCNGQKKVI LTKTLVIGQC IYTFTSLFSL MPDVAHSLAV ELCVP GLHG WATVMLLSTF CFGWVLIPAV TLIILKCLRV LTFSCSHYTN ESKFKFILEK VKIEYQKTMG SMVCDVCHHE CETAKE LES HRQSCINGQC PYCMTITEAT ESALQAHYSI CKLTGRFQEA LKKSLKKPEV KKGCYRTLGV FRYKSRCYVG LVWCLLL TC EIVIWAASA

UniProtKB: Envelopment polyprotein

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Macromolecule #2: Glycoprotein C

MacromoleculeName: Glycoprotein C / type: protein_or_peptide / ID: 2 / Number of copies: 8 / Enantiomer: LEVO
Source (natural)Organism: Orthohantavirus andesense
Molecular weightTheoretical: 58.843688 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: ETPLMESGWS DTAHGVGEIP MKTDLELDFS LPSSSSYSYR RKLTNPANKE ESIPFHFQME KQVIHAEIQP LGHWMDATFN IKTAFHCYG ACQKYSYPWQ TSKCFFEKDY QYETGWGCNP GDCPGVGTGC TACGVYLDKL KSVGKAYKII SLKYTRKVCI Q LGTEQTCK ...String:
ETPLMESGWS DTAHGVGEIP MKTDLELDFS LPSSSSYSYR RKLTNPANKE ESIPFHFQME KQVIHAEIQP LGHWMDATFN IKTAFHCYG ACQKYSYPWQ TSKCFFEKDY QYETGWGCNP GDCPGVGTGC TACGVYLDKL KSVGKAYKII SLKYTRKVCI Q LGTEQTCK HIDANDCLVT PSVKVCIVGT VSKLQPSDTL LFLGPLEQGG IILKQWCTTS CAFGDPGDIM STPSGMRCPE HT GSFRKIC GFATTPVCEY QGNTISGYKR MMATKDSFQS FNLTEPHITT NKLEWIDPDG NTRDHVNLVL NRDVSFQDLS DNP CKVDLH TQAIEGAWGS GVGFTLTCTV GLTECPSFMT SIKACDLAMC YGSTVTNLAR GSNTVKVVGK GGHSGSSFKC CHDT DCSSE GLLASAPHLE RVTGFNQIDS DKVYDDGAPP CTFKCWFTKL GEWLLGILNG NWIVVVVLVV ILILSIIMFS VLCPR RGHK KTVGSLEVLF QGPGHHHHHH HHSAWSHPQF EKGGGSGGGG SGGSAWSHPQ FEK

UniProtKB: Envelopment polyprotein

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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
GridModel: Quantifoil / Support film - Material: GOLD / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 60 sec.
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Instrument: FEI VITROBOT MARK IV

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Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K3 BIOCONTINUUM (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: 2.4 µm / Nominal defocus min: 0.9 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.37 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC (ver. 4.6.2) / Number images used: 73185
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: PROJECTION MATCHING
FSC plot (resolution estimation)

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