[English] 日本語
Yorodumi
- PDB-7k8q: Crystal structure of an anti-SARS-CoV-2 human neutralizing antibo... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7k8q
TitleCrystal structure of an anti-SARS-CoV-2 human neutralizing antibody Fab fragment, C121
Components
  • C121 Fab Heavy Chain
  • C121 Fab Light Chain
KeywordsIMMUNE SYSTEM / Human Neutralizing Antibody / SARS-CoV-2 / Receptor Binding Domain / COVID-19
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2 Å
AuthorsAbernathy, M.E. / Barnes, C.O. / Bjorkman, P.J.
Funding support United States, 2items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)P01-AI138938-S1 United States
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)P50 AI150464-13 United States
CitationJournal: Nature / Year: 2020
Title: SARS-CoV-2 neutralizing antibody structures inform therapeutic strategies.
Authors: Christopher O Barnes / Claudia A Jette / Morgan E Abernathy / Kim-Marie A Dam / Shannon R Esswein / Harry B Gristick / Andrey G Malyutin / Naima G Sharaf / Kathryn E Huey-Tubman / Yu E Lee / ...Authors: Christopher O Barnes / Claudia A Jette / Morgan E Abernathy / Kim-Marie A Dam / Shannon R Esswein / Harry B Gristick / Andrey G Malyutin / Naima G Sharaf / Kathryn E Huey-Tubman / Yu E Lee / Davide F Robbiani / Michel C Nussenzweig / Anthony P West / Pamela J Bjorkman /
Abstract: The coronavirus disease 2019 (COVID-19) pandemic presents an urgent health crisis. Human neutralizing antibodies that target the host ACE2 receptor-binding domain (RBD) of the severe acute ...The coronavirus disease 2019 (COVID-19) pandemic presents an urgent health crisis. Human neutralizing antibodies that target the host ACE2 receptor-binding domain (RBD) of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein show promise therapeutically and are being evaluated clinically. Here, to identify the structural correlates of SARS-CoV-2 neutralization, we solved eight new structures of distinct COVID-19 human neutralizing antibodies in complex with the SARS-CoV-2 spike trimer or RBD. Structural comparisons allowed us to classify the antibodies into categories: (1) neutralizing antibodies encoded by the VH3-53 gene segment with short CDRH3 loops that block ACE2 and bind only to 'up' RBDs; (2) ACE2-blocking neutralizing antibodies that bind both up and 'down' RBDs and can contact adjacent RBDs; (3) neutralizing antibodies that bind outside the ACE2 site and recognize both up and down RBDs; and (4) previously described antibodies that do not block ACE2 and bind only to up RBDs. Class 2 contained four neutralizing antibodies with epitopes that bridged RBDs, including a VH3-53 antibody that used a long CDRH3 with a hydrophobic tip to bridge between adjacent down RBDs, thereby locking the spike into a closed conformation. Epitope and paratope mapping revealed few interactions with host-derived N-glycans and minor contributions of antibody somatic hypermutations to epitope contacts. Affinity measurements and mapping of naturally occurring and in vitro-selected spike mutants in 3D provided insight into the potential for SARS-CoV-2 to escape from antibodies elicited during infection or delivered therapeutically. These classifications and structural analyses provide rules for assigning current and future human RBD-targeting antibodies into classes, evaluating avidity effects and suggesting combinations for clinical use, and provide insight into immune responses against SARS-CoV-2.
History
DepositionSep 27, 2020Deposition site: RCSB / Processing site: RCSB
Revision 1.0Oct 21, 2020Provider: repository / Type: Initial release
Revision 1.1Oct 28, 2020Group: Structure summary / Category: struct / Item: _struct.title
Revision 1.2Jan 13, 2021Group: 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 1.3Oct 18, 2023Group: 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: C121 Fab Heavy Chain
L: C121 Fab Light Chain
hetero molecules


Theoretical massNumber of molelcules
Total (without water)48,6773
Polymers48,5852
Non-polymers921
Water21612
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area3130 Å2
ΔGint-22 kcal/mol
Surface area20340 Å2
MethodPISA
Unit cell
Length a, b, c (Å)71.304, 71.304, 404.844
Angle α, β, γ (deg.)90.000, 90.000, 120.000
Int Tables number179
Space group name H-MP6522
Space group name HallP652(x,y,z+1/12)
Symmetry operation#1: x,y,z
#2: x-y,x,z+5/6
#3: y,-x+y,z+1/6
#4: -y,x-y,z+2/3
#5: -x+y,-x,z+1/3
#6: x-y,-y,-z
#7: -x,-x+y,-z+1/3
#8: -x,-y,z+1/2
#9: y,x,-z+2/3
#10: -y,-x,-z+1/6
#11: -x+y,y,-z+1/2
#12: x,x-y,-z+5/6

-
Components

#1: Antibody C121 Fab Heavy Chain


Mass: 25965.162 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): HEK293 / Production host: Homo sapiens (human)
#2: Antibody C121 Fab Light Chain


Mass: 22619.984 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): HEK293 / Production host: Homo sapiens (human)
#3: Chemical ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL / Glycerol


Mass: 92.094 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C3H8O3
#4: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 12 / 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: 3.06 Å3/Da / Density % sol: 59.77 %
Crystal growTemperature: 298 K / Method: vapor diffusion, sitting drop / pH: 5.1 / Details: 0.2 M ammonium citrate, 20% PEG3350

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SSRL / Beamline: BL12-1 / Wavelength: 1 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Jun 19, 2020
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2→39.1 Å / Num. obs: 42233 / % possible obs: 99.2 % / Redundancy: 26.3 % / Biso Wilson estimate: 47.81 Å2 / CC1/2: 0.995 / Rmerge(I) obs: 0.058 / Rpim(I) all: 0.114 / Net I/σ(I): 8.4
Reflection shellResolution: 2→2.05 Å / Rmerge(I) obs: 1.36 / Mean I/σ(I) obs: 0.6 / Num. unique obs: 2989 / CC1/2: 0.977 / Rpim(I) all: 0.81

-
Processing

Software
NameVersionClassification
PHENIX1.18.2_3874refinement
Blu-Icedata collection
XDSdata reduction
Aimlessdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB entry 5T3Z

5t3z


Resolution: 2→36.36 Å / SU ML: 0.3004 / Cross valid method: FREE R-VALUE / σ(F): 1.33 / Phase error: 26.6461
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.2431 2059 4.88 %
Rwork0.2054 40174 -
obs0.2072 42233 98.74 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 53.47 Å2
Refinement stepCycle: LAST / Resolution: 2→36.36 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3247 0 6 12 3265
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0083333
X-RAY DIFFRACTIONf_angle_d0.99564544
X-RAY DIFFRACTIONf_chiral_restr0.0616513
X-RAY DIFFRACTIONf_plane_restr0.0056577
X-RAY DIFFRACTIONf_dihedral_angle_d21.3759470
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2-2.050.32141160.31572520X-RAY DIFFRACTION94.75
2.05-2.10.38581200.32872645X-RAY DIFFRACTION98.71
2.1-2.160.351280.29042583X-RAY DIFFRACTION98.76
2.16-2.220.3451400.29512614X-RAY DIFFRACTION98.78
2.22-2.290.36781400.28832628X-RAY DIFFRACTION99
2.29-2.370.34151420.28072630X-RAY DIFFRACTION98.96
2.37-2.470.271280.25132642X-RAY DIFFRACTION99.18
2.47-2.580.32581230.26522623X-RAY DIFFRACTION97.93
2.58-2.720.27781440.2572639X-RAY DIFFRACTION99.32
2.72-2.890.2891450.25432675X-RAY DIFFRACTION99.61
2.89-3.110.27451290.25332729X-RAY DIFFRACTION99.58
3.11-3.420.27251690.23152704X-RAY DIFFRACTION99.83
3.42-3.910.23291470.18932703X-RAY DIFFRACTION98.31
3.92-4.930.15331360.14052825X-RAY DIFFRACTION99.87
4.93-36.360.20671520.16343014X-RAY DIFFRACTION98.38
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)
15.264170438024.14325641153-1.755844649023.2657813597-1.471336847593.014198880710.323563617155-0.458518354238-0.04046618088850.213122903792-0.474661763214-0.728145973102-0.2239021730580.3316749479840.02852555107340.482898265904-0.01816733515740.04514150595960.418246694439-0.06436725429150.463615044844-9.882314402485.83242885242-15.2779319426
20.6913194675640.626858491089-0.06196525570085.37286339755-0.3865763504931.167688300280.134199660838-0.0956591759889-0.2683310403760.358655308984-0.257092771582-0.331645376503-0.1413555093050.05356149290190.1440736622810.4593506667310.003834233809610.0586261038940.487909077413-0.05595495450470.380483188012-13.1224258044-4.80348868595-19.0407830616
33.121024489551.164962966310.006389583647692.9005125577-0.4192605495513.14012324804-0.01272488781990.132540647670.61325139553-0.3997023606860.0722182777635-0.180166475936-0.630626928581-0.164037769429-0.03204243731250.470252662312-0.004262364037640.06464125990560.431493844119-0.04053296537760.346528140268-16.28631726770.649690192294-28.4166816769
43.64856812349-0.6718574382330.1979266490823.686079701532.382705083861.639144376140.404894833640.0608372787249-0.0234930916268-0.143412525650.0248677532539-0.245152168595-0.2067029740470.328371093055-0.4214256678750.428535773603-0.04979216184970.09885286305170.571135115093-0.04675945697420.403620577397-6.970840595161.39481622364-24.3438328901
51.758998954330.4840503983280.2101144140175.241211514221.646631966620.7757508622020.318943984455-0.117885919704-0.008839244217910.106307971398-0.124524933804-0.8471978054850.0700327037676-0.140638995561-0.1074299564860.489543448529-0.01028194101360.08092482206340.528301860011-0.08485009203420.328543647937-17.7923286398-1.58260376662-21.7196811051
60.689855660842-0.943164893616-0.2981094355491.983279655761.38358345911.17725145662-0.1441688015660.1155670125720.166389246881-0.04727638023870.204860259548-0.09274339541960.0007339651497770.0550718681543-0.06662928262340.355710938362-0.003747170280720.05168289007230.437284093336-0.02016059000540.392530189736-18.06413833619.674345176-6.98746879353
73.29107885122-0.32228197842-1.252091521341.956207715460.5180543451364.14231199051-0.2357402391770.204815627752-0.0116142452372-0.2346950751210.0159642127348-0.3310241550410.107109558218-0.105927132986-0.01261971344650.380753722516-0.0321325509812-0.008585807718950.374838125585-0.03062301037380.512702377375-16.793362765323.51995819630.664436279234
83.51638470828-1.45604823704-0.1651931163222.442287201010.09813219570244.4506003469-0.0458926093660.6125547943030.210828293459-0.5829270986910.175692622599-0.2618157725290.281562314608-0.4174837710070.05962133677110.395052382798-0.0563140177024-0.009847979544080.382295851934-0.01781961525630.388662449339-21.151399404625.1009621144-6.68565474853
95.106000884050.816244039424-1.300469806832.255975661490.7887374851016.61677769231-0.185018331629-0.290359365657-0.2483323455280.2567876642010.223342677095-0.383260585087-0.06511573852450.49013920935-0.02266206585580.3664597489750.0413928297478-0.0794372086870.250365761277-0.001936728483960.45035336891-16.89156909726.89734957747.80681923099
104.59720486844-5.50887733931-3.056955886198.772415344771.683314546284.697294170150.594260170687-1.054251477450.07095727047961.71303625921-0.173108145586-1.09936904511-0.829385204685-0.0421398745066-0.3733016798290.670466976706-0.023109996047-0.04000637640590.458884056826-0.02991630277920.55720321367-18.631368447335.18662712211.366685653
111.256370929090.1478184427391.576792904455.50072269062-0.5331821112715.30140484440.4530261706340.3751394026990.236235840836-0.00759272870225-0.5606531823370.914473384628-0.552148535451-0.7663697170850.2098963102770.4705533549790.04857038580650.01593960684730.612736971467-0.1659815272030.690896040074-40.41606734322.68227931887-22.0632550244
122.287105793470.026407842971-0.2716500697372.941117860250.3648335312641.857315958440.107192990625-0.05786175555160.1391617431940.194822735825-0.1091049831020.457880817235-0.0883985007062-0.297998681908-0.008102359310330.3808516187990.005831283479120.0812455357070.490559427707-0.126738518060.436268923412-33.4777351877-3.97856051197-21.0153159307
131.147632488731.831990656211.136493684854.379631000863.216464083272.582736290220.263100231186-0.0904783079568-0.5510658162961.25770029555-0.4940549277550.3115984810150.583934225274-0.1263877719820.606969502030.4387688296130.02121746592260.09155623222180.466570628309-0.1088349010940.620905624312-40.746207430620.4303422789-4.09398954114
147.212258954240.7190725445380.4492075969075.599858460881.14035670313.343993309020.05027056283420.4692296852940.148320620059-0.0816395399981-0.192668749133-0.671769989033-0.305033626575-0.05331405808310.1568688298040.3146445290510.0410170804221-0.004332708764180.3488674848910.004446767156220.359289714335-30.023423863734.0026734132-7.43776068684
Refinement TLS group

Refine-ID: X-RAY DIFFRACTION

IDRefine TLS-IDSelection detailsAuth asym-IDLabel asym-IDAuth seq-IDLabel seq-ID
11chain 'H' and (resid 1 through 17 )HC1 - 171 - 17
22chain 'H' and (resid 18 through 39 )HC18 - 3918 - 39
33chain 'H' and (resid 40 through 64 )HC40 - 6440 - 65
44chain 'H' and (resid 65 through 83 )HC65 - 8366 - 87
55chain 'H' and (resid 84 through 100 )HC84 - 10088 - 104
66chain 'H' and (resid 101 through 139 )HC101 - 139116 - 149
77chain 'H' and (resid 140 through 162 )HC140 - 162150 - 172
88chain 'H' and (resid 163 through 182 )HC163 - 182173 - 192
99chain 'H' and (resid 183 through 210 )HC183 - 210193 - 220
1010chain 'H' and (resid 211 through 214 )HC211 - 214221 - 224
1111chain 'L' and (resid 1 through 23 )LD1 - 231 - 23
1212chain 'L' and (resid 24 through 104 )LD24 - 10424 - 108
1313chain 'L' and (resid 105 through 117 )LD105 - 117109 - 121
1414chain 'L' and (resid 118 through 209 )LD118 - 209122 - 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://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