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- EMDB-29294: HIV-1 envelope trimer bound to three CD4 molecules on membranes -

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Basic information

Entry
Database: EMDB / ID: EMD-29294
TitleHIV-1 envelope trimer bound to three CD4 molecules on membranes
Map data
Sample
  • Complex: HIV-1 envelope trimer bound to three CD4 molecules on membranes
KeywordsVirus-Host Complex / Glycoprotein / Cell receptor / VIRAL PROTEIN
Biological speciesHuman immunodeficiency virus 1
Methodsubtomogram averaging / cryo EM / Resolution: 15.0 Å
AuthorsLi W / Qin Z / Nand E / Grunst MW / Grover JR / Uchil PD / Mothes W
Funding support United States, 1 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)R01 AI150560 United States
CitationJournal: Nature / Year: 2023
Title: HIV-1 Env trimers asymmetrically engage CD4 receptors in membranes.
Authors: Wenwei Li / Zhuan Qin / Elizabeth Nand / Michael W Grunst / Jonathan R Grover / Julian W Bess / Jeffrey D Lifson / Michael B Zwick / Hemant D Tagare / Pradeep D Uchil / Walther Mothes /
Abstract: Human immunodeficiency virus 1 (HIV-1) infection is initiated by binding of the viral envelope glycoprotein (Env) to the cell-surface receptor CD4. Although high-resolution structures of Env in a ...Human immunodeficiency virus 1 (HIV-1) infection is initiated by binding of the viral envelope glycoprotein (Env) to the cell-surface receptor CD4. Although high-resolution structures of Env in a complex with the soluble domains of CD4 have been determined, the binding process is less understood in native membranes. Here we used cryo-electron tomography to monitor Env-CD4 interactions at the membrane-membrane interfaces formed between HIV-1 and CD4-presenting virus-like particles. Env-CD4 complexes organized into clusters and rings, bringing the opposing membranes closer together. Env-CD4 clustering was dependent on capsid maturation. Subtomogram averaging and classification revealed that Env bound to one, two and finally three CD4 molecules, after which Env adopted an open state. Our data indicate that asymmetric HIV-1 Env trimers bound to one and two CD4 molecules are detectable intermediates during virus binding to host cell membranes, which probably has consequences for antibody-mediated immune responses and vaccine immunogen design.
History
DepositionDec 23, 2022-
Header (metadata) releaseNov 8, 2023-
Map releaseNov 8, 2023-
UpdateDec 13, 2023-
Current statusDec 13, 2023Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_29294.png

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Map

FileDownload / File: emd_29294.map.gz / Format: CCP4 / Size: 15.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
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AxesZ (Sec.)Y (Row.)X (Col.)
2.7 Å/pix.
x 160 pix.
= 432. Å		2.7 Å/pix.
x 160 pix.
= 432. Å		2.7 Å/pix.
x 160 pix.
= 432. Å

Surface

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Images are generated by Spider.

Voxel sizeX=Y=Z: 2.7 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.1
Minimum - Maximum-0.26841488 - 0.30999276
Average (Standard dev.)-0.000000000017061 (±0.043359585)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin-80-80-80
Dimensions160160160
Spacing160160160
CellA=B=C: 432.0 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #1

Fileemd_29294_half_map_1.map
Projections & Slices
AxesZYX

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Half map: #2

Fileemd_29294_half_map_2.map
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Sample components

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Entire : HIV-1 envelope trimer bound to three CD4 molecules on membranes

EntireName: HIV-1 envelope trimer bound to three CD4 molecules on membranes
Components
  • Complex: HIV-1 envelope trimer bound to three CD4 molecules on membranes

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Supramolecule #1: HIV-1 envelope trimer bound to three CD4 molecules on membranes

SupramoleculeName: HIV-1 envelope trimer bound to three CD4 molecules on membranes
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2
Source (natural)Organism: Human immunodeficiency virus 1

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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: 7.4
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Specialist opticsPhase plate: VOLTA PHASE PLATE / Energy filter - Name: GIF Quantum LS / Energy filter - Slit width: 20 eV
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 3.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsC2 aperture diameter: 50.0 µm / Illumination mode: OTHER / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 0.5 µm / Nominal defocus min: 0.0 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Final reconstructionNumber classes used: 1953 / Applied symmetry - Point group: C1 (asymmetric) / Resolution.type: BY AUTHOR / Resolution: 15.0 Å / Resolution method: FSC 0.143 CUT-OFF / Number subtomograms used: 168
ExtractionNumber tomograms: 168 / Number images used: 1953
Final angle assignmentType: OTHER
FSC plot (resolution estimation)

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