[English] 日本語
Yorodumi
- PDB-7lok: Structure of CD4 mimetic M48U1 in complex with BG505 SOSIP.664 HI... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7lok
TitleStructure of CD4 mimetic M48U1 in complex with BG505 SOSIP.664 HIV-1 Env trimer and 17b Fab
Components
  • 17b Fab Heavy Chain
  • 17b Fab Light Chain
  • Envelope Glycoprotein BG505 SOSIP.664 gp41
  • Envelope glycoprotein BG505 SOSIP.664 gp120
  • M48U1
KeywordsVIRAL PROTEIN/IMMUNE SYSTEM / HIV-1 / fusion / entry / membrane / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex
Function / homology
Function and homology information


positive regulation of plasma membrane raft polarization / positive regulation of establishment of T cell polarity / positive regulation of receptor clustering / actin filament reorganization / host cell endosome membrane / mitigation of host immune response by virus / clathrin-dependent endocytosis of virus by host cell / viral protein processing / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane ...positive regulation of plasma membrane raft polarization / positive regulation of establishment of T cell polarity / positive regulation of receptor clustering / actin filament reorganization / host cell endosome membrane / mitigation of host immune response by virus / clathrin-dependent endocytosis of virus by host cell / viral protein processing / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane / viral envelope / virion attachment to host cell / host cell plasma membrane / virion membrane / structural molecule activity / integral component of membrane / identical protein binding / plasma membrane
Envelope glycoprotein GP120 / Envelope glycoprotein Gp160 / Gp120 core superfamily / Human immunodeficiency virus 1, envelope glycoprotein Gp120 / Retroviral envelope protein GP41-like
Envelope glycoprotein gp160 / polysac:dmanpa1-3dmanpa1-6[dmanpa1-3]dmanpb1-4dglcpnacb1-4dglcpnacb1-roh: / polysac:dmanpa1-3dmanpa1-6dmanpb1-4dglcpnacb1-4dglcpnacb1-roh: / polysac:dmanpa1-3dmanpb1-4dglcpnacb1-4dglcpnacb1-roh:
Biological speciesHuman immunodeficiency virus 1
Homo sapiens (human)
Leiurus quinquestriatus hebraeus (scorpion)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.9 Å
AuthorsJette, C.A. / Bjorkman, P.J.
Funding support United States, 2items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)2 P50 AI150464 United States
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)HIVRAD P01 AI100148 United States
CitationJournal: Nat Commun / Year: 2021
Title: Cryo-EM structures of HIV-1 trimer bound to CD4-mimetics BNM-III-170 and M48U1 adopt a CD4-bound open conformation.
Authors: Claudia A Jette / Christopher O Barnes / Sharon M Kirk / Bruno Melillo / Amos B Smith / Pamela J Bjorkman /
Abstract: Human immunodeficiency virus-1 (HIV-1), the causative agent of AIDS, impacts millions of people. Entry into target cells is mediated by the HIV-1 envelope (Env) glycoprotein interacting with host ...Human immunodeficiency virus-1 (HIV-1), the causative agent of AIDS, impacts millions of people. Entry into target cells is mediated by the HIV-1 envelope (Env) glycoprotein interacting with host receptor CD4, which triggers conformational changes allowing binding to a coreceptor and subsequent membrane fusion. Small molecule or peptide CD4-mimetic drugs mimic CD4's Phe43 interaction with Env by inserting into the conserved Phe43 pocket on Env subunit gp120. Here, we present single-particle cryo-EM structures of CD4-mimetics BNM-III-170 and M48U1 bound to a BG505 native-like Env trimer plus the CD4-induced antibody 17b at 3.7 Å and 3.9 Å resolution, respectively. CD4-mimetic-bound BG505 exhibits canonical CD4-induced conformational changes including trimer opening, formation of the 4-stranded gp120 bridging sheet, displacement of the V1V2 loop, and formation of a compact and elongated gp41 HR1C helical bundle. We conclude that CD4-induced structural changes on both gp120 and gp41 Env subunits are induced by binding to the gp120 Phe43 pocket.
Validation Report
SummaryFull reportAbout validation report
History
DepositionFeb 10, 2021Deposition site: RCSB / Processing site: RCSB
Revision 1.0Apr 14, 2021Provider: repository / Type: Initial release

-
Structure visualization

Movie
  • Deposited structure unit
  • Imaged by Jmol
  • Download
  • Superimposition on EM map
  • EMDB-23465
  • Imaged by UCSF Chimera
  • Download
Movie viewer
Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
C: Envelope glycoprotein BG505 SOSIP.664 gp120
D: Envelope Glycoprotein BG505 SOSIP.664 gp41
A: Envelope glycoprotein BG505 SOSIP.664 gp120
B: Envelope Glycoprotein BG505 SOSIP.664 gp41
J: 17b Fab Light Chain
K: 17b Fab Heavy Chain
L: 17b Fab Light Chain
M: 17b Fab Heavy Chain
G: M48U1
H: M48U1
F: Envelope Glycoprotein BG505 SOSIP.664 gp41
E: Envelope glycoprotein BG505 SOSIP.664 gp120
I: M48U1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)325,00224
Polymers320,49913
Non-polymers4,50211
Water0
1


TypeNameSymmetry operationNumber
identity operation1_5551

-
Components

-
Protein , 2 types, 6 molecules CAEDBF

#1: Protein Envelope glycoprotein BG505 SOSIP.664 gp120


Mass: 53864.086 Da / Num. of mol.: 3 / Mutation: BG505 SOSIP.664
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Human immunodeficiency virus 1 / Gene: env / Cell line (production host): HEK293 / Production host: Homo sapiens (human) / References: UniProt: Q2N0S6
#2: Protein Envelope Glycoprotein BG505 SOSIP.664 gp41


Mass: 17146.482 Da / Num. of mol.: 3 / Mutation: BG505 SOSIP.664
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Human immunodeficiency virus 1 / Gene: env / Cell line (production host): HEK293 / Production host: Homo sapiens (human) / References: UniProt: Q2N0S6

-
Protein/peptide , 1 types, 3 molecules GHI

#5: Protein/peptide M48U1


Mass: 3056.804 Da / Num. of mol.: 3 / Source method: obtained synthetically
Source: (synth.) Leiurus quinquestriatus hebraeus (scorpion)

-
Antibody , 2 types, 4 molecules JLKM

#3: Antibody 17b Fab Light Chain


Mass: 23399.898 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): HEK293 / Production host: Homo sapiens (human)
#4: Antibody 17b Fab Heavy Chain


Mass: 25748.771 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): HEK293 / Production host: Homo sapiens (human)

-
Sugars , 4 types, 11 molecules

#6: Polysaccharide alpha-D-mannopyranose-(1-3)-alpha-D-mannopyranose-(1-6)-[alpha-D-mannopyranose-(1-3)]beta-D- ...alpha-D-mannopyranose-(1-3)-alpha-D-mannopyranose-(1-6)-[alpha-D-mannopyranose-(1-3)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose


Type: oligosaccharide / Mass: 1072.964 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
DescriptorTypeProgram
DManpa1-3DManpa1-6[DManpa1-3]DManpb1-4DGlcpNAcb1-4DGlcpNAcb1-ROHGlycam Condensed SequenceGMML 1.0
WURCS=2.0/3,6,5/[a2122h-1b_1-5_2*NCC/3=O][a1122h-1b_1-5][a1122h-1a_1-5]/1-1-2-3-3-3/a4-b1_b4-c1_c3-d1_c6-e1_e3-f1WURCSPDB2Glycan 1.1.0
[][D-1-deoxy-GlcpNAc]{[(4+1)][b-D-GlcpNAc]{[(4+1)][b-D-Manp]{[(3+1)][a-D-Manp]{}[(6+1)][a-D-Manp]{[(3+1)][a-D-Manp]{}}}}}LINUCSPDB-CARE
#7: Polysaccharide alpha-D-mannopyranose-(1-3)-alpha-D-mannopyranose-(1-6)-beta-D-mannopyranose-(1-4)-2-acetamido-2- ...alpha-D-mannopyranose-(1-3)-alpha-D-mannopyranose-(1-6)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose


Type: oligosaccharide / Mass: 910.823 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
DescriptorTypeProgram
DManpa1-3DManpa1-6DManpb1-4DGlcpNAcb1-4DGlcpNAcb1-ROHGlycam Condensed SequenceGMML 1.0
WURCS=2.0/3,5,4/[a2122h-1b_1-5_2*NCC/3=O][a1122h-1b_1-5][a1122h-1a_1-5]/1-1-2-3-3/a4-b1_b4-c1_c6-d1_d3-e1WURCSPDB2Glycan 1.1.0
[][D-1-deoxy-GlcpNAc]{[(4+1)][b-D-GlcpNAc]{[(4+1)][b-D-Manp]{[(6+1)][a-D-Manp]{[(3+1)][a-D-Manp]{}}}}}LINUCSPDB-CARE
#8: Polysaccharide alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1- ...alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose


Type: oligosaccharide / Mass: 748.682 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
DescriptorTypeProgram
DManpa1-3DManpb1-4DGlcpNAcb1-4DGlcpNAcb1-ROHGlycam Condensed SequenceGMML 1.0
WURCS=2.0/3,4,3/[a2122h-1b_1-5_2*NCC/3=O][a1122h-1b_1-5][a1122h-1a_1-5]/1-1-2-3/a4-b1_b4-c1_c3-d1WURCSPDB2Glycan 1.1.0
[][D-1-deoxy-GlcpNAc]{[(4+1)][b-D-GlcpNAc]{[(4+1)][b-D-Manp]{[(3+1)][a-D-Manp]{}}}}LINUCSPDB-CARE
#9: Sugar
ChemComp-NAG / 2-acetamido-2-deoxy-beta-D-glucopyranose / N-acetyl-beta-D-glucosamine / 2-acetamido-2-deoxy-beta-D-glucose / 2-acetamido-2-deoxy-D-glucose / 2-acetamido-2-deoxy-glucose / N-ACETYL-D-GLUCOSAMINE / N-Acetylglucosamine


Type: D-saccharide, beta linking / Mass: 221.208 Da / Num. of mol.: 8
Source method: isolated from a genetically manipulated source
Formula: C8H15NO6
IdentifierTypeProgram
DGlcpNAcbCONDENSED IUPAC CARBOHYDRATE SYMBOLGMML 1.0
N-acetyl-b-D-glucopyranosamineCOMMON NAMEGMML 1.0
b-D-GlcpNAcIUPAC CARBOHYDRATE SYMBOLPDB-CARE 1.0
GlcNAcSNFG CARBOHYDRATE SYMBOLGMML 1.0

-
Details

Has ligand of interestY

-
Experimental details

-
Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

-
Sample preparation

Component
IDNameTypeDetailsEntity IDParent-IDSource
1Human immunodeficiency virus 1Subtypes of HIVCOMPLEXBG505 SOSIP.664 Env trimer in complex with CD4 mimetic M48U1 and 17b Fab#1-#50MULTIPLE SOURCES
217b antibody FabCOMPLEX#3-#41RECOMBINANT
3M48U1COMPLEXSynthetic peptide, CD4 mimetic#51SYNTHETIC
4BG505 SOSIP.664 EnvCOMPLEX#1-#21RECOMBINANT
Molecular weight
IDEntity assembly-IDExperimental value
11
21NO
31
41NO
Source (natural)
IDEntity assembly-IDOrganismNcbi tax-IDStrain
32Homo sapiens (human)9606
43Leiurus quinquestriatus hebraeus (scorpion)6884
54Human immunodeficiency virus 111676BG505
Source (recombinant)
IDEntity assembly-IDOrganismNcbi tax-IDCell
32Homo sapiens (human)9606HEK293
54Homo sapiens (human)9606HEK293
Details of virus
IDEntity assembly-IDEmptyEnveloped
11YESNO
22
33
44
Buffer solutionpH: 8
Buffer component
IDConc.NameFormulaBuffer-ID
120 mMTris1
2100 mMSodium chlorideNaClSodium chloride1
SpecimenConc.: 1.4 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES / Details: This sample was monodisperse
VitrificationInstrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 295.5 K

-
Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: SPOT SCAN
Electron lensMode: BRIGHT FIELDBright-field microscopy
Specimen holderModel: FEI TITAN KRIOS AUTOGRID HOLDER
Image recordingElectron dose: 60 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) / Num. of grids imaged: 1 / Num. of real images: 2688

-
Processing

SoftwareName: PHENIX / Version: 1.17.1_3660: / Classification: refinement
EM software
IDNameVersionCategory
2SerialEMimage acquisition
7UCSF Chimeramodel fitting
8PHENIX1.18model fitting
10PHENIX1.18model refinement
14RELION3D reconstruction
CTF correctionType: PHASE FLIPPING ONLY
SymmetryPoint symmetry: C1 (asymmetric)
3D reconstructionResolution: 3.9 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 263981 / Symmetry type: POINT
Atomic model building
IDPDB-ID3D fitting-ID
16U0L1
24JZZ1
32NXY1
Refine LS restraints
Refinement-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.00616395
ELECTRON MICROSCOPYf_angle_d1.15422261
ELECTRON MICROSCOPYf_dihedral_angle_d16.2065970
ELECTRON MICROSCOPYf_chiral_restr0.1042587
ELECTRON MICROSCOPYf_plane_restr0.0132791

+
About Yorodumi

-
News

-
Aug 12, 2020. New: Covid-19 info

New: Covid-19 info

  • 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. New: 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. (see PDBe EMDB page)
  • 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 at PDBe / 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. See below links for details.
  • 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

+
Jun 16, 2017. Omokage search with filter

Omokage search with filter

  • Result of Omokage search can be filtered by keywords and the database types

Related info.:Omokage search

Read more

-
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.

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