[English] 日本語
Yorodumi
- PDB-6oz9: Ebola virus glycoprotein in complex with EBOV-520 Fab -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6oz9
TitleEbola virus glycoprotein in complex with EBOV-520 Fab
Components
  • (EBOV-520 Fab ...) x 2
  • Envelope glycoprotein
  • Small secreted glycoprotein sGP
KeywordsVIRAL PROTEIN/Immune system / Glycoprotein / antibody / Fab / VIRAL PROTEIN / VIRAL PROTEIN-Immune system complex
Function / homology
Function and homology information


host cell endoplasmic reticulum / viral budding from plasma membrane / clathrin-dependent endocytosis of virus by host cell / suppression by virus of host tetherin activity / host cell cytoplasm / entry receptor-mediated virion attachment to host cell / symbiont entry into host cell / membrane raft / fusion of virus membrane with host endosome membrane / viral envelope ...host cell endoplasmic reticulum / viral budding from plasma membrane / clathrin-dependent endocytosis of virus by host cell / suppression by virus of host tetherin activity / host cell cytoplasm / entry receptor-mediated virion attachment to host cell / symbiont entry into host cell / membrane raft / fusion of virus membrane with host endosome membrane / viral envelope / lipid binding / host cell plasma membrane / virion membrane / extracellular region / identical protein binding / membrane
Similarity search - Function
Filoviruses glycoprotein, extracellular domain / Filoviruses glycoprotein / Filovirus glycoprotein / Immunoglobulins / Immunoglobulin-like / Sandwich / Mainly Beta
Similarity search - Domain/homology
Small secreted glycoprotein sGP / Envelope glycoprotein / Envelope glycoprotein
Similarity search - Component
Biological speciesEbola virus
Homo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 3.462 Å
AuthorsMilligan, J.C. / Altman, P.X. / Hui, S. / Hastie, K.M. / Gilchuk, P. / Crowe, J.E. / Saphire, E.O.
Funding support United States, 3items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)U19 109762 United States
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)R01AI132204 United States
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)5T32AI007354-27 United States
CitationJournal: Immunity / Year: 2020
Title: Analysis of a Therapeutic Antibody Cocktail Reveals Determinants for Cooperative and Broad Ebolavirus Neutralization.
Authors: Pavlo Gilchuk / Charles D Murin / Jacob C Milligan / Robert W Cross / Chad E Mire / Philipp A Ilinykh / Kai Huang / Natalia Kuzmina / Pilar X Altman / Sean Hui / Bronwyn M Gunn / Aubrey L ...Authors: Pavlo Gilchuk / Charles D Murin / Jacob C Milligan / Robert W Cross / Chad E Mire / Philipp A Ilinykh / Kai Huang / Natalia Kuzmina / Pilar X Altman / Sean Hui / Bronwyn M Gunn / Aubrey L Bryan / Edgar Davidson / Benjamin J Doranz / Hannah L Turner / Tanwee Alkutkar / Robin Flinko / Chiara Orlandi / Robert Carnahan / Rachel Nargi / Robin G Bombardi / Megan E Vodzak / Sheng Li / Adaora Okoli / Morris Ibeawuchi / Benjamin Ohiaeri / George K Lewis / Galit Alter / Alexander Bukreyev / Erica Ollmann Saphire / Thomas W Geisbert / Andrew B Ward / James E Crowe /
Abstract: Structural principles underlying the composition of protective antiviral monoclonal antibody (mAb) cocktails are poorly defined. Here, we exploited antibody cooperativity to develop a therapeutic mAb ...Structural principles underlying the composition of protective antiviral monoclonal antibody (mAb) cocktails are poorly defined. Here, we exploited antibody cooperativity to develop a therapeutic mAb cocktail against Ebola virus. We systematically analyzed the antibody repertoire in human survivors and identified a pair of potently neutralizing mAbs that cooperatively bound to the ebolavirus glycoprotein (GP). High-resolution structures revealed that in a two-antibody cocktail, molecular mimicry was a major feature of mAb-GP interactions. Broadly neutralizing mAb rEBOV-520 targeted a conserved epitope on the GP base region. mAb rEBOV-548 bound to a glycan cap epitope, possessed neutralizing and Fc-mediated effector function activities, and potentiated neutralization by rEBOV-520. Remodeling of the glycan cap structures by the cocktail enabled enhanced GP binding and virus neutralization. The cocktail demonstrated resistance to virus escape and protected non-human primates (NHPs) against Ebola virus disease. These data illuminate structural principles of antibody cooperativity with implications for development of antiviral immunotherapeutics.
History
DepositionMay 15, 2019Deposition site: RCSB / Processing site: RCSB
Revision 1.0Mar 11, 2020Provider: repository / Type: Initial release
Revision 2.0Jul 29, 2020Group: Atomic model / Data collection ...Atomic model / Data collection / Derived calculations / Structure summary
Category: atom_site / chem_comp ...atom_site / chem_comp / entity / pdbx_branch_scheme / pdbx_chem_comp_identifier / pdbx_entity_branch / pdbx_entity_branch_descriptor / pdbx_entity_branch_link / pdbx_entity_branch_list / pdbx_entity_nonpoly / pdbx_nonpoly_scheme / pdbx_struct_assembly_gen / struct_asym / struct_conn / struct_site / struct_site_gen
Item: _atom_site.B_iso_or_equiv / _atom_site.Cartn_x ..._atom_site.B_iso_or_equiv / _atom_site.Cartn_x / _atom_site.Cartn_y / _atom_site.Cartn_z / _atom_site.auth_asym_id / _atom_site.auth_atom_id / _atom_site.auth_comp_id / _atom_site.auth_seq_id / _atom_site.label_asym_id / _atom_site.label_atom_id / _atom_site.label_comp_id / _atom_site.label_entity_id / _atom_site.type_symbol / _chem_comp.name / _pdbx_struct_assembly_gen.asym_id_list / _struct_conn.pdbx_role / _struct_conn.ptnr1_auth_asym_id / _struct_conn.ptnr1_auth_seq_id / _struct_conn.ptnr1_label_asym_id / _struct_conn.ptnr2_auth_asym_id / _struct_conn.ptnr2_auth_seq_id / _struct_conn.ptnr2_label_asym_id
Description: Carbohydrate remediation / Provider: repository / Type: Remediation

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Small secreted glycoprotein sGP
B: Envelope glycoprotein
L: EBOV-520 Fab light chain
H: EBOV-520 Fab heavy chain
hetero molecules


Theoretical massNumber of molelcules
Total (without water)78,0346
Polymers77,3564
Non-polymers6792
Water00
1
A: Small secreted glycoprotein sGP
B: Envelope glycoprotein
L: EBOV-520 Fab light chain
H: EBOV-520 Fab heavy chain
hetero molecules

A: Small secreted glycoprotein sGP
B: Envelope glycoprotein
L: EBOV-520 Fab light chain
H: EBOV-520 Fab heavy chain
hetero molecules

A: Small secreted glycoprotein sGP
B: Envelope glycoprotein
L: EBOV-520 Fab light chain
H: EBOV-520 Fab heavy chain
hetero molecules


Theoretical massNumber of molelcules
Total (without water)234,10318
Polymers232,06712
Non-polymers2,0366
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation5_555z,x,y1
crystal symmetry operation9_555y,z,x1
Unit cell
Length a, b, c (Å)217.970, 217.970, 217.970
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number213
Space group name H-MP4132

-
Components

-
Protein , 2 types, 2 molecules AB

#1: Protein Small secreted glycoprotein sGP


Mass: 17196.516 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Ebola virus
Gene: sGP, DF49_53415gpsGP, DF49_53416gpsGP, DF49_53417gpsGP, DF49_53418gpsGP, DF49_53419gpsGP, DF49_53420gpsGP, DF49_53421gpsGP, DF49_53422gpsGP, DF49_53423gpsGP, DF49_53424gpsGP, DF49_53425gpsGP, ...Gene: sGP, DF49_53415gpsGP, DF49_53416gpsGP, DF49_53417gpsGP, DF49_53418gpsGP, DF49_53419gpsGP, DF49_53420gpsGP, DF49_53421gpsGP, DF49_53422gpsGP, DF49_53423gpsGP, DF49_53424gpsGP, DF49_53425gpsGP, DF49_53426gpsGP, DH33_45401gpsGP, DH33_45402gpsGP
Variant: Mayinga / Cell line (production host): S2 / Production host: Drosophila melanogaster (fruit fly) / References: UniProt: A0A0E3H7K0, UniProt: Q05320*PLUS
#2: Protein Envelope glycoprotein


Mass: 12650.368 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Ebola virus / Gene: GP, DH33_45401gpGP / Variant: Mayinga / Cell line (production host): S2 / Production host: Drosophila melanogaster (fruit fly) / References: UniProt: A0A0E3H7K2, UniProt: Q05320*PLUS

-
Antibody , 2 types, 2 molecules LH

#3: Antibody EBOV-520 Fab light chain


Mass: 23434.941 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human)
#4: Antibody EBOV-520 Fab heavy chain


Mass: 24073.971 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human)

-
Sugars / Non-polymers , 2 types, 2 molecules

#5: Polysaccharide beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta- ...beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose


Type: oligosaccharide / Mass: 586.542 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
DescriptorTypeProgram
DManpb1-4DGlcpNAcb1-4DGlcpNAcb1-Glycam Condensed SequenceGMML 1.0
WURCS=2.0/2,3,2/[a2122h-1b_1-5_2*NCC/3=O][a1122h-1b_1-5]/1-1-2/a4-b1_b4-c1WURCSPDB2Glycan 1.1.0
[]{[(4+1)][b-D-GlcpNAc]{[(4+1)][b-D-GlcpNAc]{[(4+1)][b-D-Manp]{}}}}LINUCSPDB-CARE
#6: Chemical ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C3H8O3

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

-
Sample preparation

CrystalDensity Matthews: 5.54 Å3/Da / Density % sol: 77.79 %
Crystal growTemperature: 295 K / Method: vapor diffusion, sitting drop / Details: 0.1 M HEPES pH 7.0 and 1.4 M Ammonium sulfate

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 23-ID-D / Wavelength: 1 Å
DetectorType: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Jun 13, 2018
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 3.462→77.064 Å / Num. obs: 23638 / % possible obs: 99.19 % / Redundancy: 36.7 % / Net I/σ(I): 18.9
Reflection shellResolution: 3.462→3.586 Å / Num. unique obs: 2296

-
Processing

Software
NameVersionClassification
PHENIX1.15rc1_3420refinement
MOSFLMdata reduction
Aimlessdata scaling
PHENIXphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 3.462→77.064 Å / SU ML: 0.35 / Cross valid method: FREE R-VALUE / σ(F): 0 / Phase error: 20.8 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2345 1984 8.46 %
Rwork0.1991 --
obs0.2021 23452 99.21 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Refinement stepCycle: LAST / Resolution: 3.462→77.064 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms5402 0 6 0 5408
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0035540
X-RAY DIFFRACTIONf_angle_d0.5897554
X-RAY DIFFRACTIONf_dihedral_angle_d3.9643254
X-RAY DIFFRACTIONf_chiral_restr0.043855
X-RAY DIFFRACTIONf_plane_restr0.004973
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
3.4625-3.5490.26571320.26461440X-RAY DIFFRACTION97
3.549-3.6450.3181410.25611479X-RAY DIFFRACTION98
3.645-3.75230.27821360.23651489X-RAY DIFFRACTION98
3.7523-3.87340.27091380.22321505X-RAY DIFFRACTION99
3.8734-4.01180.25261380.22531502X-RAY DIFFRACTION99
4.0118-4.17240.22921380.19451494X-RAY DIFFRACTION99
4.1724-4.36230.20231440.17731543X-RAY DIFFRACTION100
4.3623-4.59230.20081400.15961510X-RAY DIFFRACTION100
4.5923-4.87990.21241410.16251532X-RAY DIFFRACTION100
4.8799-5.25660.19091430.16671538X-RAY DIFFRACTION100
5.2566-5.78550.20861430.18281553X-RAY DIFFRACTION100
5.7855-6.62220.2251460.19971569X-RAY DIFFRACTION100
6.6222-8.34170.24711470.20191601X-RAY DIFFRACTION100
8.3417-77.08310.25141570.21471713X-RAY DIFFRACTION100
Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL11 (°2)L12 (°2)L13 (°2)L22 (°2)L23 (°2)L33 (°2)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T11 (Å2)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)T33 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
10.5577-0.13790.26510.32270.17770.3386-0.1218-0.0455-0.09240.23480.12610.24470.0518-0.4431-0.00010.7794-0.05380.05990.7939-0.0230.6387-1.6204-3.7838-24.297
20.7390.0952-0.16650.4926-0.56210.57380.14020.05080.1571-0.1512-0.1018-0.31030.00810.00860.00010.7583-0.03050.05470.7832-0.03320.709114.797615.5799-11.7241
30.95750.875-0.62130.7645-0.56980.3856-0.09510.006-0.00560.1835-0.0252-0.10360.02060.11320.00010.598-0.0428-0.02020.58260.00210.619613.19839.8395-11.9006
40.7440.9265-0.03011.0732-0.00850.5097-0.23450.37060.00320.27560.2032-0.06160.06660.277200.63160.04110.14050.83130.07370.849315.6297-6.3346-15.653
50.33320.4990.11040.63520.29390.45730.0269-0.17490.2056-0.2137-0.0970.0272-0.227-0.0757-0.00010.51950.0225-0.03630.50890.0380.5735-4.5358-3.6131-20.2286
60.5370.15990.11430.9696-0.95591.0443-0.0020.1592-0.0239-0.099-0.1083-0.0347-0.1664-0.103200.6352-0.01030.10880.64290.03330.684426.947511.3589-47.6862
71.33510.54560.3941.548-0.59750.4342-0.23060.21260.3662-0.35150.0183-0.1167-0.01260.1482-0.00010.66520.08920.26540.9795-0.02520.696159.77049.2846-63.1566
80.0847-0.11190.16270.1402-0.20930.2945-0.028-0.2883-0.38150.36090.107-0.2642-0.38680.41420.00021.08180.06740.08810.82570.00960.960742.5327-8.8184-37.882
90.77670.33280.52420.9115-0.21570.5736-0.1739-0.16490.0165-0.15510.0093-0.61750.1603-0.3762-0.00041.01390.14290.24730.64990.01640.674532.6512-4.1187-36.5044
100.66240.6098-0.07960.58460.1220.5098-0.0215-0.1549-0.36560.4757-0.01330.04610.7027-0.1177-0.00011.03250.07810.13450.61370.0490.710930.2235-5.8518-35.9416
110.0696-0.02430.1880.1161-0.13740.56310.23360.3738-0.25160.5661-0.37570.23430.0963-0.11440.00030.81680.28820.10330.7287-0.0680.979744.5762-6.2495-43.2322
120.11160.0209-0.11250.09850.13130.28760.3456-0.2929-0.812-0.8718-0.6710.30010.71890.42880.00070.9383-0.19920.07611.56330.41431.830666.32545.9647-52.5586
130.1641-0.1291-0.05060.4205-0.27610.3082-0.0891-0.3893-0.20970.4073-0.00110.13660.14931.26350.00021.22890.12280.09771.3199-0.08361.372756.97953.7396-49.3004
140.1618-0.3502-0.46320.76440.98851.278-0.8103-0.99940.48120.43560.3685-0.1511.56440.9537-0.01631.2336-0.2693-0.14211.64090.20781.750264.11386.0244-42.3253
150.00050.01550.00620.03290.03770.06030.5728-1.07150.66580.3160.8048-0.42140.52-0.13130.00161.464-0.03-0.22971.61930.24782.070969.97075.3044-44.2003
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1chain 'A' and (resid 31 through 73 )
2X-RAY DIFFRACTION2chain 'A' and (resid 74 through 124 )
3X-RAY DIFFRACTION3chain 'A' and (resid 125 through 188 )
4X-RAY DIFFRACTION4chain 'B' and (resid 503 through 543 )
5X-RAY DIFFRACTION5chain 'B' and (resid 544 through 615 )
6X-RAY DIFFRACTION6chain 'L' and (resid 1 through 102 )
7X-RAY DIFFRACTION7chain 'L' and (resid 103 through 214 )
8X-RAY DIFFRACTION8chain 'H' and (resid 1 through 17 )
9X-RAY DIFFRACTION9chain 'H' and (resid 18 through 52 )
10X-RAY DIFFRACTION10chain 'H' and (resid 53 through 110 )
11X-RAY DIFFRACTION11chain 'H' and (resid 111 through 130 )
12X-RAY DIFFRACTION12chain 'H' and (resid 131 through 156 )
13X-RAY DIFFRACTION13chain 'H' and (resid 157 through 196 )
14X-RAY DIFFRACTION14chain 'H' and (resid 197 through 215 )
15X-RAY DIFFRACTION15chain 'H' and (resid 216 through 226 )

+
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://pdbjlvh1.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