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- EMDB-16511: HERV-K Gag immature lattice -

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Basic information

Entry
Database: EMDB / ID: EMD-16511
TitleHERV-K Gag immature lattice
Map data
Sample
  • Virus: Human endogenous retrovirus K
    • Protein or peptide: Gag protein
KeywordsC6 symmetry / endogenous retrovirus / VIRUS LIKE PARTICLE
Function / homology
Function and homology information


viral process / nucleic acid binding / structural molecule activity / zinc ion binding
Similarity search - Function
Beta-retroviral matrix protein / Beta-retroviral matrix superfamily / Retroviral GAG p10 protein / GAG-polyprotein viral zinc-finger / : / gag protein p24 N-terminal domain / Retroviral nucleocapsid Gag protein p24, C-terminal domain / Gag protein p24 C-terminal domain / Retrovirus capsid, C-terminal / Retroviral matrix protein ...Beta-retroviral matrix protein / Beta-retroviral matrix superfamily / Retroviral GAG p10 protein / GAG-polyprotein viral zinc-finger / : / gag protein p24 N-terminal domain / Retroviral nucleocapsid Gag protein p24, C-terminal domain / Gag protein p24 C-terminal domain / Retrovirus capsid, C-terminal / Retroviral matrix protein / Retrovirus capsid, N-terminal / zinc finger / Zinc knuckle / Zinc finger, CCHC-type superfamily / Zinc finger, CCHC-type / Zinc finger CCHC-type profile.
Similarity search - Domain/homology
Biological speciesHuman endogenous retrovirus K
Methodsubtomogram averaging / cryo EM / Resolution: 3.2 Å
AuthorsKrebs A-S / Liu H-F / Zhou Y / Rey JS / Levintov L / Perilla JR / Bartesaghi A / Zhang P
Funding support United Kingdom, 1 items
OrganizationGrant numberCountry
Wellcome Trust206422/Z/17/Z United Kingdom
CitationJournal: bioRxiv / Year: 2023
Title: Molecular architecture and conservation of an immature human endogenous retrovirus.
Authors: Anna-Sophia Krebs / Hsuan-Fu Liu / Ye Zhou / Juan S Rey / Lev Levintov / Juan Shen / Andrew Howe / Juan R Perilla / Alberto Bartesaghi / Peijun Zhang /
Abstract: A significant part of the human genome consists of endogenous retroviruses sequences. Human endogenous retrovirus K (HERV-K) is the most recently acquired endogenous retrovirus, is activated and ...A significant part of the human genome consists of endogenous retroviruses sequences. Human endogenous retrovirus K (HERV-K) is the most recently acquired endogenous retrovirus, is activated and expressed in many cancers and amyotrophic lateral sclerosis and possibly contributes to the aging process. To understand the molecular architecture of endogenous retroviruses, we determined the structure of immature HERV-K from native virus-like particles (VLPs) using cryo-electron tomography and subtomogram averaging (cryoET STA). The HERV-K VLPs show a greater distance between the viral membrane and immature capsid lattice, correlating with the presence of additional peptides, SP1 and p15, between the capsid (CA) and matrix (MA) proteins compared to the other retroviruses. The resulting cryoET STA map of the immature HERV-K capsid at 3.2 Å resolution shows a hexamer unit oligomerized through a 6-helix bundle which is further stabilized by a small molecule in the same way as the IP6 in immature HIV-1 capsid. The HERV-K immature CA hexamer assembles into the immature lattice via highly conserved dimmer and trimer interfaces, whose interactions were further detailed through all-atom molecular dynamics simulations and supported by mutational studies. A large conformational change mediated by the flexible linker between the N-terminal and the C-terminal domains of CA occurs between the immature and the mature HERV-K capsid protein, analogous to HIV-1. Comparison between HERV-K and other retroviral immature capsid structures reveals a highly conserved mechanism for the assembly and maturation of retroviruses across genera and evolutionary time.
History
DepositionJan 23, 2023-
Header (metadata) releaseFeb 1, 2023-
Map releaseFeb 1, 2023-
UpdateJul 24, 2024-
Current statusJul 24, 2024Processing site: PDBe / Status: Released

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Structure visualization

Supplemental images

Downloads & links

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Map

FileDownload / File: emd_16511.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.5 Å/pix.
x 256 pix.
= 384.768 Å
1.5 Å/pix.
x 256 pix.
= 384.768 Å
1.5 Å/pix.
x 256 pix.
= 384.768 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.503 Å
Density
Contour LevelBy AUTHOR: 0.0736
Minimum - Maximum-0.9319716 - 1.1975625
Average (Standard dev.)0.00013992414 (±0.03085037)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions256256256
Spacing256256256
CellA=B=C: 384.768 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #2

Fileemd_16511_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Half map: #1

Fileemd_16511_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Sample components

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Entire : Human endogenous retrovirus K

EntireName: Human endogenous retrovirus K
Components
  • Virus: Human endogenous retrovirus K
    • Protein or peptide: Gag protein

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Supramolecule #1: Human endogenous retrovirus K

SupramoleculeName: Human endogenous retrovirus K / type: virus / ID: 1 / Parent: 0 / Macromolecule list: all / Details: Gag protein, not cleaved / NCBI-ID: 45617 / Sci species name: Human endogenous retrovirus K / Sci species strain: HERV-K con / Virus type: VIRUS-LIKE PARTICLE / Virus isolate: OTHER / Virus enveloped: Yes / Virus empty: Yes
Host (natural)Organism: Homo sapiens (human)
Virus shellShell ID: 1 / Name: CA-NC

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Macromolecule #1: Gag protein

MacromoleculeName: Gag protein / type: protein_or_peptide / ID: 1 / Number of copies: 6 / Enantiomer: LEVO
Source (natural)Organism: Human endogenous retrovirus K
Molecular weightTheoretical: 74.069219 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MGQTKSKIKS KYASYLSFIK ILLKRGGVKV STKNLIKLFQ IIEQFCPWFP EQGTLDLKDW KRIGKELKQA GRKGNIIPLT VWNDWAIIK AALEPFQTEE DSVSVSDAPG SCIIDCNENT RKKSQKETEG LHCEYVAEPV MAQSTQNVDY NQLQEVIYPE T LKLEGKGP ...String:
MGQTKSKIKS KYASYLSFIK ILLKRGGVKV STKNLIKLFQ IIEQFCPWFP EQGTLDLKDW KRIGKELKQA GRKGNIIPLT VWNDWAIIK AALEPFQTEE DSVSVSDAPG SCIIDCNENT RKKSQKETEG LHCEYVAEPV MAQSTQNVDY NQLQEVIYPE T LKLEGKGP ELVGPSESKP RGTSPLPAGQ VPVTLQPQKQ VKENKTQPPV AYQYWPPAEL QYRPPPESQY GYPGMPPAPQ GR APYPQPP TRRLNPTAPP SRQGSELHEI IDKSRKEGDT EAWQFPVTLE PMPPGEGAQE GEPPTVEARY KSFSIKMLKD MKE GVKQYG PNSPYMRTLL DSIAHGHRLI PYDWEILAKS SLSPSQFLQF KTWWIDGVQE QVRRNRAANP PVNIDADQLL GIGQ NWSTI SQQALMQNEA IEQVRAICLR AWEKIQDPGS TCPSFNTVRQ GSKEPYPDFV ARLQDVAQKS IADEKARKVI VELMA YENA NPECQSAIKP LKGKVPAGSD VISEYVKACD GIGGAMHKAM LMAQAITGVV LGGQVRTFGG KCYNCGQIGH LKKNCP VLN KQNITIQATT TGREPPDLCP RCKKGKHWAS QCRSKFDKNG QPLSGNEQRG QPQAPQQTGA FPIQPFVPQG FQGQQPP LS QVFQGISQLP QYNNCPPPQA AVQQ

UniProtKB: Gag protein

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Experimental details

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Structure determination

Methodcryo EM
Processingsubtomogram averaging
Aggregation stateparticle

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Sample preparation

BufferpH: 8 / Details: OptiPrep in STE buffer
GridModel: EMS Lacey Carbon / Material: COPPER / Mesh: 300 / Pretreatment - Type: GLOW DISCHARGE
VitrificationCryogen name: ETHANE / Instrument: LEICA EM GP

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Specialist opticsEnergy filter - Name: TFS Selectris / Energy filter - Slit width: 5 eV
Image recordingFilm or detector model: FEI FALCON IV (4k x 4k) / Average exposure time: 1.17 sec. / Average electron dose: 3.1 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 5.0 µm / Nominal defocus min: 2.0 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Final reconstructionApplied symmetry - Point group: C6 (6 fold cyclic) / Resolution.type: BY AUTHOR / Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Number subtomograms used: 188111
ExtractionNumber tomograms: 124 / Number images used: 274994
Final angle assignmentType: OTHER

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