[English] 日本語
Yorodumi
- PDB-7k3q: An ultra-potent human neutralizing antibody locks the SARS-CoV-2 ... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7k3q
TitleAn ultra-potent human neutralizing antibody locks the SARS-CoV-2 spike in the closed conformation
Components
  • Fab fragment of S2E12 monoclonal antibody, heavy chain
  • Fab fragment of S2E12 monoclonal antibody, light chain
KeywordsIMMUNE SYSTEM / SARS-CoV-2 / neutralizing mAb / ANTIVIRAL PROTEIN
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 1.38 Å
AuthorsSnell, G. / Czudnochowski, N. / Ng, C.
CitationJournal: Science / Year: 2020
Title: Ultrapotent human antibodies protect against SARS-CoV-2 challenge via multiple mechanisms.
Authors: M Alejandra Tortorici / Martina Beltramello / Florian A Lempp / Dora Pinto / Ha V Dang / Laura E Rosen / Matthew McCallum / John Bowen / Andrea Minola / Stefano Jaconi / Fabrizia Zatta / ...Authors: M Alejandra Tortorici / Martina Beltramello / Florian A Lempp / Dora Pinto / Ha V Dang / Laura E Rosen / Matthew McCallum / John Bowen / Andrea Minola / Stefano Jaconi / Fabrizia Zatta / Anna De Marco / Barbara Guarino / Siro Bianchi / Elvin J Lauron / Heather Tucker / Jiayi Zhou / Alessia Peter / Colin Havenar-Daughton / Jason A Wojcechowskyj / James Brett Case / Rita E Chen / Hannah Kaiser / Martin Montiel-Ruiz / Marcel Meury / Nadine Czudnochowski / Roberto Spreafico / Josh Dillen / Cindy Ng / Nicole Sprugasci / Katja Culap / Fabio Benigni / Rana Abdelnabi / Shi-Yan Caroline Foo / Michael A Schmid / Elisabetta Cameroni / Agostino Riva / Arianna Gabrieli / Massimo Galli / Matteo S Pizzuto / Johan Neyts / Michael S Diamond / Herbert W Virgin / Gyorgy Snell / Davide Corti / Katja Fink / David Veesler /
Abstract: Efficient therapeutic options are needed to control the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has caused more than 922,000 fatalities as of 13 September 2020. We ...Efficient therapeutic options are needed to control the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has caused more than 922,000 fatalities as of 13 September 2020. We report the isolation and characterization of two ultrapotent SARS-CoV-2 human neutralizing antibodies (S2E12 and S2M11) that protect hamsters against SARS-CoV-2 challenge. Cryo-electron microscopy structures show that S2E12 and S2M11 competitively block angiotensin-converting enzyme 2 (ACE2) attachment and that S2M11 also locks the spike in a closed conformation by recognition of a quaternary epitope spanning two adjacent receptor-binding domains. Antibody cocktails that include S2M11, S2E12, or the previously identified S309 antibody broadly neutralize a panel of circulating SARS-CoV-2 isolates and activate effector functions. Our results pave the way to implement antibody cocktails for prophylaxis or therapy, circumventing or limiting the emergence of viral escape mutants.
History
DepositionSep 12, 2020Deposition site: RCSB / Processing site: RCSB
Revision 1.0Oct 7, 2020Provider: repository / Type: Initial release
Revision 1.1Dec 2, 2020Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation_author.identifier_ORCID
Revision 1.2Apr 3, 2024Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
H: Fab fragment of S2E12 monoclonal antibody, heavy chain
L: Fab fragment of S2E12 monoclonal antibody, light chain
hetero molecules


Theoretical massNumber of molelcules
Total (without water)47,7515
Polymers47,5352
Non-polymers2163
Water5,873326
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: surface plasmon resonance
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area4320 Å2
ΔGint-25 kcal/mol
Surface area19610 Å2
MethodPISA
Unit cell
Length a, b, c (Å)58.014, 85.722, 86.306
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121

-
Components

#1: Antibody Fab fragment of S2E12 monoclonal antibody, heavy chain


Mass: 23988.887 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Production host: Cricetulus griseus (Chinese hamster)
#2: Antibody Fab fragment of S2E12 monoclonal antibody, light chain


Mass: 23546.127 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Production host: Cricetulus griseus (Chinese hamster)
#3: Chemical ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C3H8O3
#4: Chemical ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL


Mass: 62.068 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C2H6O2
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 326 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestN

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.26 Å3/Da / Density % sol: 45.51 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop
Details: 0.2 M Magnesium chloride hexahydrate, 0.1 M TRIS pH 8.5, 30% (w/v) PEG 4000 Condition A1 of Molecular Dimensions SG1 HT-96 Eco Screen

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X10SA / Wavelength: 1 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Sep 6, 2020
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 1.38→48.15 Å / Num. obs: 89367 / % possible obs: 99.3 % / Redundancy: 13.1 % / CC1/2: 0.999 / Rmerge(I) obs: 0.059 / Rpim(I) all: 0.024 / Rrim(I) all: 0.064 / Net I/σ(I): 19.1
Reflection shellResolution: 1.38→1.4 Å / Rmerge(I) obs: 2.115 / Mean I/σ(I) obs: 1.2 / Num. unique obs: 3868 / CC1/2: 0.74 / Rpim(I) all: 0.881 / Rrim(I) all: 2.295 / % possible all: 87.8

-
Phasing

PhasingMethod: molecular replacement

-
Processing

Software
NameVersionClassification
REFMAC5.8.0258refinement
XSCALEdata scaling
PHASERphasing
PDB_EXTRACT3.25data extraction
XDSdata reduction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: homology model

Resolution: 1.38→40 Å / Cor.coef. Fo:Fc: 0.967 / Cor.coef. Fo:Fc free: 0.961 / SU B: 2.673 / SU ML: 0.052 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.065 / ESU R Free: 0.063 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : WITH TLS ADDED
RfactorNum. reflection% reflectionSelection details
Rfree0.215 4458 5.2 %RANDOM
Rwork0.1993 ---
obs0.2002 84581 99.72 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: BABINET MODEL WITH MASK
Displacement parametersBiso max: 69.53 Å2 / Biso mean: 27.198 Å2 / Biso min: 20.28 Å2
Baniso -1Baniso -2Baniso -3
1--0.73 Å20 Å20 Å2
2--1.63 Å2-0 Å2
3----0.9 Å2
Refinement stepCycle: final / Resolution: 1.38→40 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3339 0 14 326 3679
Biso mean--44.62 35.78 -
Num. residues----442
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0040.0133500
X-RAY DIFFRACTIONr_bond_other_d0.0010.0173138
X-RAY DIFFRACTIONr_angle_refined_deg1.2261.6464781
X-RAY DIFFRACTIONr_angle_other_deg1.2371.5687342
X-RAY DIFFRACTIONr_dihedral_angle_1_deg7.3755466
X-RAY DIFFRACTIONr_dihedral_angle_2_deg30.25722.349149
X-RAY DIFFRACTIONr_dihedral_angle_3_deg12.35115563
X-RAY DIFFRACTIONr_dihedral_angle_4_deg18.2951517
X-RAY DIFFRACTIONr_chiral_restr0.0460.2472
X-RAY DIFFRACTIONr_gen_planes_refined0.0040.023954
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02721
LS refinement shellResolution: 1.38→1.414 Å / Rfactor Rfree error: 0
RfactorNum. reflection% reflection
Rfree0.531 347 -
Rwork0.531 6004 -
obs--97.07 %
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)
11.90230.6827-0.6620.7727-0.24181.69370.047-0.08210.0196-0.0173-0.0104-0.00650.03510.0556-0.03660.0179-0.0063-0.00490.0587-0.01120.0056-17.834-58.3832.214
21.1750.35890.42261.22531.4713.19670.00160.1038-0.0915-0.03890.0973-0.1541-0.0670.1525-0.09890.01640.00250.00810.0794-0.01470.04742.558-34.33515.921
31.9459-0.4958-0.61321.93541.13062.04940.09990.12320.0601-0.1116-0.1570.0677-0.1677-0.2050.05720.02270.00810.00180.0847-0.02190.0218-33.245-45.36210.562
43.58260.8549-1.32811.5231-0.25521.56350.01430.27250.1738-0.1820.0413-0.094-0.09420.0447-0.05560.0610.00850.00980.0967-0.00180.0299-6.286-21.91311.376
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1H1 - 125
2X-RAY DIFFRACTION2H126 - 226
3X-RAY DIFFRACTION3L1 - 107
4X-RAY DIFFRACTION4L108 - 213

+
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