[English] 日本語
Yorodumi
- EMDB-20150: CD4- and 17-bound HIV-1 Env B41 SOSIP in complex with small molec... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-20150
TitleCD4- and 17-bound HIV-1 Env B41 SOSIP in complex with small molecule GO35
Map dataSharpened map
Sample
  • Complex: CD4- and 17b-bound HIV-1 Env B41 SOSIP in complex with small molecule GO35
    • Complex: 17b fragment antigen binding
    • Protein or peptide: Envelope glycoprotein gp160
    • Protein or peptide: Envelope glycoprotein gp41
    • Protein or peptide: T-cell surface glycoprotein CD4
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
  • Ligand: [3'-(5-methyl-1,3,4-oxadiazol-2-yl)[1,1'-biphenyl]-3-yl](piperidin-1-yl)methanone
KeywordsHIV-1 / Env / CD4 / receptor-bound state / small molecule / fusion inhibitor / VIRAL PROTEIN / VIRAL PROTEIN-Immune System complex
Function / homology
Function and homology information


helper T cell enhancement of adaptive immune response / interleukin-16 binding / interleukin-16 receptor activity / maintenance of protein location in cell / T cell selection / MHC class II protein binding / positive regulation of kinase activity / cellular response to granulocyte macrophage colony-stimulating factor stimulus / interleukin-15-mediated signaling pathway / positive regulation of monocyte differentiation ...helper T cell enhancement of adaptive immune response / interleukin-16 binding / interleukin-16 receptor activity / maintenance of protein location in cell / T cell selection / MHC class II protein binding / positive regulation of kinase activity / cellular response to granulocyte macrophage colony-stimulating factor stimulus / interleukin-15-mediated signaling pathway / positive regulation of monocyte differentiation / Nef Mediated CD4 Down-regulation / Alpha-defensins / regulation of T cell activation / Other interleukin signaling / extracellular matrix structural constituent / T cell receptor complex / enzyme-linked receptor protein signaling pathway / Translocation of ZAP-70 to Immunological synapse / Phosphorylation of CD3 and TCR zeta chains / macrophage differentiation / regulation of calcium ion transport / Generation of second messenger molecules / T cell differentiation / Co-inhibition by PD-1 / positive regulation of protein kinase activity / Binding and entry of HIV virion / coreceptor activity / positive regulation of plasma membrane raft polarization / positive regulation of receptor clustering / positive regulation of interleukin-2 production / positive regulation of calcium-mediated signaling / cell surface receptor protein tyrosine kinase signaling pathway / protein tyrosine kinase binding / host cell endosome membrane / Vpu mediated degradation of CD4 / clathrin-coated endocytic vesicle membrane / calcium-mediated signaling / positive regulation of T cell activation / MHC class II protein complex binding / transmembrane signaling receptor activity / Downstream TCR signaling / Cargo recognition for clathrin-mediated endocytosis / signaling receptor activity / Clathrin-mediated endocytosis / positive regulation of protein phosphorylation / virus receptor activity / defense response to Gram-negative bacterium / clathrin-dependent endocytosis of virus by host cell / adaptive immune response / positive regulation of canonical NF-kappaB signal transduction / positive regulation of viral entry into host cell / early endosome / cell surface receptor signaling pathway / positive regulation of ERK1 and ERK2 cascade / positive regulation of MAPK cascade / cell adhesion / viral protein processing / immune response / membrane raft / endoplasmic reticulum lumen / external side of plasma membrane / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane / lipid binding / viral envelope / endoplasmic reticulum membrane / protein kinase binding / positive regulation of DNA-templated transcription / virion attachment to host cell / host cell plasma membrane / virion membrane / structural molecule activity / enzyme binding / signal transduction / protein homodimerization activity / zinc ion binding / identical protein binding / membrane / plasma membrane
Similarity search - Function
CD4, extracellular / T cell CD4 receptor C-terminal region / CD4, extracellular / T cell CD4 receptor C terminal region / T-cell surface antigen CD4 / Immunoglobulin C2-set / Immunoglobulin C2-set domain / Immunoglobulin / Immunoglobulin domain / Envelope glycoprotein Gp160 ...CD4, extracellular / T cell CD4 receptor C-terminal region / CD4, extracellular / T cell CD4 receptor C terminal region / T-cell surface antigen CD4 / Immunoglobulin C2-set / Immunoglobulin C2-set domain / Immunoglobulin / Immunoglobulin domain / Envelope glycoprotein Gp160 / Retroviral envelope protein / Retroviral envelope protein GP41-like / Gp120 core superfamily / Envelope glycoprotein GP120 / Human immunodeficiency virus 1, envelope glycoprotein Gp120 / Immunoglobulin subtype 2 / Immunoglobulin C-2 Type / Immunoglobulin V-Type / Immunoglobulin V-set domain / Immunoglobulin subtype / Immunoglobulin / Ig-like domain profile. / Immunoglobulin-like domain / Immunoglobulin-like domain superfamily / Immunoglobulin-like fold
Similarity search - Domain/homology
Envelope glycoprotein gp160 / Envelope glycoprotein gp160 / T-cell surface glycoprotein CD4
Similarity search - Component
Biological speciesHuman immunodeficiency virus 1 / Homo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.5 Å
AuthorsOzorowski G / Torres JL
Funding support United States, 2 items
OrganizationGrant numberCountry
Other private109718-63-RKNT United States
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)R01GM069832 United States
Citation
Journal: Cell Rep / Year: 2020
Title: A Strain-Specific Inhibitor of Receptor-Bound HIV-1 Targets a Pocket near the Fusion Peptide.
Authors: Gabriel Ozorowski / Jonathan L Torres / Diogo Santos-Martins / Stefano Forli / Andrew B Ward /
Abstract: Disruption of viral fusion represents a viable, albeit under-explored, target for HIV therapeutics. Here, while studying the receptor-bound envelope glycoprotein conformation by cryoelectron ...Disruption of viral fusion represents a viable, albeit under-explored, target for HIV therapeutics. Here, while studying the receptor-bound envelope glycoprotein conformation by cryoelectron microscopy (cryo-EM), we identify a pocket near the base of the trimer containing a bound detergent molecule and perform in silico drug screening by using a library of drug-like and commercially available molecules. After down-selection, we solve cryo-EM structures that validate the binding of two small molecule hits in very similar manners to the predicted binding poses, including interactions with aromatic residues within the fusion peptide. One of the molecules demonstrates low micromolar inhibition of the autologous virus by using a very rare phenylalanine in the fusion peptide and stabilizing the surrounding region. This work demonstrates that small molecules can target the fusion process, providing an additional target for anti-HIV therapeutics, and highlights the need to explore how fusion peptide sequence variations affect receptor-mediated conformational states across diverse HIV strains.
#1: Journal: Biorxiv / Year: 2020
Title: A strain-specific inhibitor of receptor-bound HIV-1 targets a pocket near the fusion peptide and offers a template for drug design
Authors: Ozorowski G / Torres JL / Santos-Martins D / Forli S / Ward AB
History
DepositionApr 25, 2019-
Header (metadata) releaseJun 12, 2019-
Map releaseOct 21, 2020-
UpdateNov 13, 2024-
Current statusNov 13, 2024Processing site: RCSB / Status: Released

-
Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 0.4
  • Imaged by UCSF Chimera
  • Download
  • Surface view colored by cylindrical radius
  • Surface level: 0.4
  • Imaged by UCSF Chimera
  • Download
  • Surface view with fitted model
  • Atomic models: PDB-6opn
  • Surface level: 0.4
  • Imaged by UCSF Chimera
  • Download
  • Simplified surface model + fitted atomic model
  • Atomic modelsPDB-6opn
  • Imaged by Jmol
  • Download
Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

emd_20150.png

Downloads & links

-
Map

FileDownload / File: emd_20150.map.gz / Format: CCP4 / Size: 91.1 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.)
1.03 Å/pix.
x 288 pix.
= 296.64 Å		1.03 Å/pix.
x 288 pix.
= 296.64 Å		1.03 Å/pix.
x 288 pix.
= 296.64 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.03 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.4 / Movie #1: 0.4
Minimum - Maximum-0.7688051 - 1.6918817
Average (Standard dev.)-0.00014661852 (±0.063546844)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions288288288
Spacing288288288
CellA=B=C: 296.63998 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z1.031.031.03
M x/y/z288288288
origin x/y/z0.0000.0000.000
length x/y/z296.640296.640296.640
α/β/γ90.00090.00090.000
start NX/NY/NZ9482110
NX/NY/NZ11313776
MAP C/R/S123
start NC/NR/NS000
NC/NR/NS288288288
D min/max/mean-0.7691.692-0.000

-
Supplemental data

-
Mask #1

Fileemd_20150_msk_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: Half map A

Fileemd_20150_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_20150_half_map_2.map
AnnotationHalf map B
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : CD4- and 17b-bound HIV-1 Env B41 SOSIP in complex with small mole...

EntireName: CD4- and 17b-bound HIV-1 Env B41 SOSIP in complex with small molecule GO35
Components
  • Complex: CD4- and 17b-bound HIV-1 Env B41 SOSIP in complex with small molecule GO35
    • Complex: 17b fragment antigen binding
    • Protein or peptide: Envelope glycoprotein gp160
    • Protein or peptide: Envelope glycoprotein gp41
    • Protein or peptide: T-cell surface glycoprotein CD4
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
  • Ligand: [3'-(5-methyl-1,3,4-oxadiazol-2-yl)[1,1'-biphenyl]-3-yl](piperidin-1-yl)methanone

-
Supramolecule #1: CD4- and 17b-bound HIV-1 Env B41 SOSIP in complex with small mole...

SupramoleculeName: CD4- and 17b-bound HIV-1 Env B41 SOSIP in complex with small molecule GO35
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3
Source (natural)Organism: Human immunodeficiency virus 1
Molecular weightTheoretical: 50 KDa

-
Supramolecule #2: 17b fragment antigen binding

SupramoleculeName: 17b fragment antigen binding / type: complex / ID: 2 / Parent: 1
Details: 17b Fab added to aid in particle tumbling and initial alignments. Most of the Fab was masked out during final refinements to increase resolution of particle core and small molecule binding pocket.

-
Macromolecule #1: Envelope glycoprotein gp160

MacromoleculeName: Envelope glycoprotein gp160 / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Human immunodeficiency virus 1
Molecular weightTheoretical: 58.872902 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MDAMKRGLCC VLLLCGAVFV SPSQEIHARF RRGARAAKKW VTVYYGVPVW KEATTTLFCA SDAKAYDTEV HNVWATHACV PTDPNPQEI VLGNVTENFN MWKNNMVEQM HEDIISLWDQ SLKPCVKLTP LCVTLNCNNV NTNNTNNSTN ATISDWEKME T GEMKNCSF ...String:
MDAMKRGLCC VLLLCGAVFV SPSQEIHARF RRGARAAKKW VTVYYGVPVW KEATTTLFCA SDAKAYDTEV HNVWATHACV PTDPNPQEI VLGNVTENFN MWKNNMVEQM HEDIISLWDQ SLKPCVKLTP LCVTLNCNNV NTNNTNNSTN ATISDWEKME T GEMKNCSF NVTTSIRDKI KKEYALFYKL DVVPLENKNN INNTNITNYR LINCNTSVIT QACPKVSFEP IPIHYCAPAG FA ILKCNSK TFNGSGPCTN VSTVQCTHGI RPVVSTQLLL NGSLAEEEIV IRSENITDNA KTIIVQLNEA VEINCTRPNN NTR KSIHIG PGRAFYATGD IIGNIRQAHC NISKARWNET LGQIVAKLEE QFPNKTIIFN HSSGGDPEIV THSFNCGGEF FYCN TTPLF NSTWNNTRTD DYPTGGEQNI TLQCRIKQII NMWQGVGKAM YAPPIRGQIR CSSNITGLLL TRDGGRDQNG TETFR PGGG NMRDNWRSEL YKYKVVKIEP LGIAPTACKR RVVQRRRRRR

UniProtKB: Envelope glycoprotein gp160

-
Macromolecule #2: Envelope glycoprotein gp41

MacromoleculeName: Envelope glycoprotein gp41 / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Human immunodeficiency virus 1 / Strain: B41
Molecular weightTheoretical: 17.357824 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
AVGLGAFILG FLGAAGSTMG AASMALTVQA RLLLSGIVQQ QNNLLRAPEA QQHMLQLTVW GIKQLQARVL AVERYLRDQQ LLGIWGCSG KIICCTNVPW NDSWSNKTIN EIWDNMTWMQ WEKEIDNYTQ HIYTLLEVSQ IQQEKNEQEL LELD

UniProtKB: Envelope glycoprotein gp160

-
Macromolecule #3: T-cell surface glycoprotein CD4

MacromoleculeName: T-cell surface glycoprotein CD4 / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 23.039172 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: METDTLLLWV LLLWVPGSTG KKVVLGKKGD TVELTCTASQ KKSIQFHWKN SNQIKILGNQ GSFLTKGPSK LNDRADSRRS LWDQGNFPL IIKNLKIEDS DTYICEVEDQ KEEVQLLVFG LTANSDTHLL QGQSLTLTLE SPPGSSPSVQ CRSPRGKNIQ G GKTLSVSQ ...String:
METDTLLLWV LLLWVPGSTG KKVVLGKKGD TVELTCTASQ KKSIQFHWKN SNQIKILGNQ GSFLTKGPSK LNDRADSRRS LWDQGNFPL IIKNLKIEDS DTYICEVEDQ KEEVQLLVFG LTANSDTHLL QGQSLTLTLE SPPGSSPSVQ CRSPRGKNIQ G GKTLSVSQ LELQDSGTWT CTVLQNQKKV EFKIDIVVLA GGSGHHHHHH

UniProtKB: T-cell surface glycoprotein CD4

-
Macromolecule #6: 2-acetamido-2-deoxy-beta-D-glucopyranose

MacromoleculeName: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 6 / Number of copies: 27 / Formula: NAG
Molecular weightTheoretical: 221.208 Da
Chemical component information

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

-
Macromolecule #7: [3'-(5-methyl-1,3,4-oxadiazol-2-yl)[1,1'-biphenyl]-3-yl](piperidi...

MacromoleculeName: [3'-(5-methyl-1,3,4-oxadiazol-2-yl)[1,1'-biphenyl]-3-yl](piperidin-1-yl)methanone
type: ligand / ID: 7 / Number of copies: 3 / Formula: N07
Molecular weightTheoretical: 347.41 Da
Chemical component information

ChemComp-N07:
[3'-(5-methyl-1,3,4-oxadiazol-2-yl)[1,1'-biphenyl]-3-yl](piperidin-1-yl)methanone

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

Concentration6 mg/mL
BufferpH: 7.4
Component:
ConcentrationName
50.0 mMTris
150.0 mMNaCl
1.0 %(v/v)dimethyl sulfoxide
0.005 mMlauryl maltose neopentyl glycol

Details: Detergent (LMNG) added shortly (<5 minutes) prior to grid freezing using an 8X concentrated stock.
GridModel: C-flat-2/2 / Material: COPPER / Mesh: 400 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: PLASMA CLEANING / Pretreatment - Time: 10 sec.
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 283 K / Instrument: FEI VITROBOT MARK IV
DetailsComplex of CD4- and 17b-bound B41 SOSIP was SEC purified and GO35 was diluted 1:100 into the complex and incubated for 1 hr prior to grid freezing.

-
Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Number real images: 1285 / Average exposure time: 12.5 sec. / Average electron dose: 60.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsC2 aperture diameter: 70.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.2 µm / Nominal defocus min: 0.6 µm / Nominal magnification: 29000
Sample stageSpecimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

+
Image processing

Startup modelType of model: EMDB MAP
EMDB ID:

8715

Final reconstructionNumber classes used: 1 / Applied symmetry - Point group: C3 (3 fold cyclic) / Resolution.type: BY AUTHOR / Resolution: 3.5 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC (ver. 2) / Software - details: Non-uniform refinement
Details: FSC resolution estimation calculated using CryoSparc 2 and Relion 3.0
Number images used: 30415
Initial angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC (ver. 2)
Final angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC (ver. 2)
Final 3D classificationNumber classes: 3 / Avg.num./class: 33000 / Software - Name: cryoSPARC (ver. 2)
FSC plot (resolution estimation)

-
Atomic model buiding 1

Initial modelPDB ID:

5vn3


Chain - Source name: PDB / Chain - Initial model type: experimental model
RefinementSpace: REAL / Protocol: FLEXIBLE FIT
Output model

PDB-6opn:
CD4- and 17-bound HIV-1 Env B41 SOSIP in complex with small molecule GO35

+
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