[English] 日本語
Yorodumi
- PDB-7r74: Crystal structure of llama VHH antibody in complex with HIV-1 HXB... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7r74
TitleCrystal structure of llama VHH antibody in complex with HIV-1 HXBC2 gp120 core
Components
  • Antibody C8 VHH domain
  • Glycoprotein 120
KeywordsIMMUNE SYSTEM / Llama / antibody / VHH / HIV-1 / gp120
Biological speciesHuman immunodeficiency virus 1
Lama glama (llama)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 2.76 Å
AuthorsZhou, T. / Kwong, P.D.
CitationJournal: Structure / Year: 2022
Title: Structural basis for llama nanobody recognition and neutralization of HIV-1 at the CD4-binding site.
Authors: Tongqing Zhou / Lei Chen / Jason Gorman / Shuishu Wang / Young D Kwon / Bob C Lin / Mark K Louder / Reda Rawi / Erik-Stephane D Stancofski / Yongping Yang / Baoshan Zhang / Anna Forsman ...Authors: Tongqing Zhou / Lei Chen / Jason Gorman / Shuishu Wang / Young D Kwon / Bob C Lin / Mark K Louder / Reda Rawi / Erik-Stephane D Stancofski / Yongping Yang / Baoshan Zhang / Anna Forsman Quigley / Laura E McCoy / Lucy Rutten / Theo Verrips / Robin A Weiss / / Nicole A Doria-Rose / Lawrence Shapiro / Peter D Kwong /
Abstract: Nanobodies can achieve remarkable neutralization of genetically diverse pathogens, including HIV-1. To gain insight into their recognition, we determined crystal structures of four llama nanobodies ...Nanobodies can achieve remarkable neutralization of genetically diverse pathogens, including HIV-1. To gain insight into their recognition, we determined crystal structures of four llama nanobodies (J3, A12, C8, and D7), all of which targeted the CD4-binding site, in complex with the HIV-1 envelope (Env) gp120 core, and determined a cryoelectron microscopy (cryo-EM) structure of J3 with the Env trimer. Crystal and cryo-EM structures of J3 complexes revealed this nanobody to mimic binding to the prefusion-closed trimer for the primary site of CD4 recognition as well as a secondary quaternary site. In contrast, crystal structures of A12, C8, and D7 with gp120 revealed epitopes that included portions of the gp120 inner domain, inaccessible on the prefusion-closed trimer. Overall, these structures explain the broad and potent neutralization of J3 and limited neutralization of A12, C8, and D7, which utilized binding modes incompatible with the neutralization-targeted prefusion-closed conformation of Env.
History
DepositionJun 24, 2021Deposition site: RCSB / Processing site: RCSB
Revision 1.0Mar 30, 2022Provider: repository / Type: Initial release
Revision 1.1Aug 3, 2022Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_ASTM / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year
Revision 1.2Oct 18, 2023Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Glycoprotein 120
B: Antibody C8 VHH domain
C: Glycoprotein 120
D: Antibody C8 VHH domain
hetero molecules


Theoretical massNumber of molelcules
Total (without water)109,02222
Polymers105,0404
Non-polymers3,98218
Water1,45981
1
A: Glycoprotein 120
D: Antibody C8 VHH domain
hetero molecules


Theoretical massNumber of molelcules
Total (without water)54,51111
Polymers52,5202
Non-polymers1,9919
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area4880 Å2
ΔGint12 kcal/mol
Surface area20430 Å2
MethodPISA
2
B: Antibody C8 VHH domain
C: Glycoprotein 120
hetero molecules


Theoretical massNumber of molelcules
Total (without water)54,51111
Polymers52,5202
Non-polymers1,9919
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area5080 Å2
ΔGint14 kcal/mol
Surface area19990 Å2
MethodPISA
Unit cell
Length a, b, c (Å)121.077, 87.403, 91.581
Angle α, β, γ (deg.)90.000, 109.120, 90.000
Int Tables number5
Space group name H-MC121

-
Components

#1: Protein Glycoprotein 120


Mass: 39830.789 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Details: The extended core of HIV-1 gp120 from strain HXBc2 / Source: (gene. exp.) Human immunodeficiency virus 1 / Plasmid: pVRC8400 / Cell line (production host): HEK 293F / Production host: Homo sapiens (human)
#2: Antibody Antibody C8 VHH domain


Mass: 12689.152 Da / Num. of mol.: 2 / Fragment: VHH domain
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Lama glama (llama) / Plasmid: pVRC8400 / Cell line (production host): 293F / Production host: Homo sapiens (human)
#3: 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.: 18 / Source method: obtained synthetically / 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
#4: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 81 / 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: 2.18 Å3/Da / Density % sol: 43.56 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / Details: 1.0 M Li2SO4 and 100 mM HEPES pH 7.5

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 22-ID / Wavelength: 1 Å
DetectorType: MAR scanner 300 mm plate / Detector: IMAGE PLATE / Date: Oct 31, 2017
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.75→50 Å / Num. obs: 21712 / % possible obs: 94 % / Redundancy: 3.2 % / Biso Wilson estimate: 49.49 Å2 / Rmerge(I) obs: 0.139 / Χ2: 1.064 / Net I/σ(I): 8.6 / Num. measured all: 69593
Reflection shell
Resolution (Å)Redundancy (%)Rmerge(I) obsNum. unique obsΧ2Diffraction-ID% possible all
2.75-2.81.70.3685721.185150.2
2.8-2.851.90.2987851.07168.1
2.85-2.920.3318951.023179.3
2.9-2.962.30.30310370.994188.7
2.96-3.032.50.29710771.042195.9
3.03-3.12.70.27211501.027198.6
3.1-3.172.90.28511221.086199.3
3.17-3.263.10.25111671.096199.8
3.26-3.363.30.24211521.097199.9
3.36-3.463.40.21911521.071100
3.46-3.593.60.20311391.063199.5
3.59-3.733.70.18211461.107199.9
3.73-3.93.70.16911601.106199.7
3.9-4.113.70.13811561.067199.7
4.11-4.363.70.12111601.091199.9
4.36-4.73.70.11511351.054199.8
4.7-5.173.70.09811491.019199.9
5.17-5.923.70.09711821.098199.8
5.92-7.463.70.09511751.047199.8
7.46-503.50.11212010.9781100

-
Phasing

PhasingMethod: molecular replacement

-
Processing

Software
NameVersionClassification
HKL-2000data reduction
SCALEPACKdata scaling
PHASERphasing
PHENIX1.19-4092refinement
PDB_EXTRACT3.27data extraction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 3TMF

3tmf
PDB Unreleased entry


Resolution: 2.76→49.56 Å / SU ML: 0.37 / Cross valid method: THROUGHOUT / σ(F): 1.34 / Phase error: 29.97 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2699 1103 5.09 %
Rwork0.2116 20581 -
obs0.2145 21684 93.16 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso max: 121.11 Å2 / Biso mean: 51.3368 Å2 / Biso min: 18.55 Å2
Refinement stepCycle: final / Resolution: 2.76→49.56 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms6426 0 252 81 6759
Biso mean--71.65 43.7 -
Num. residues----829
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / Total num. of bins used: 8

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkNum. reflection all% reflection obs (%)
2.76-2.890.34910.29051576166758
2.89-3.040.36171270.26672418254589
3.04-3.230.35911440.24192749289399
3.23-3.480.31711360.237627542890100
3.48-3.830.27711690.199327302899100
3.83-4.380.25061400.17727742914100
4.38-5.520.2041450.176127622907100
5.52-49.560.24941510.227928182969100
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)
17.1616-1.0302-1.37110.05310.15041.80140.0722-0.45090.7794-0.03390.03-0.0445-0.2676-0.2769-0.10810.26390.04040.01620.4634-0.03020.4064-7.3691-42.64430.4373
22.8877-1.13130.31265.53681.03493.25810.14550.86130.2113-0.5882-0.13780.23560.0201-0.0498-0.02390.2554-0.0322-0.03670.64870.11110.3378-15.5268-42.43688.2056
32.346-0.2178-0.18120.7159-0.41341.76670.16580.51050.227-0.1833-0.00670.23670.0601-0.4071-0.0990.23630.0151-0.01830.38290.02770.3552-18.2259-43.510318.2898
43.28450.6257-0.2555.5633-1.22833.0534-0.0939-0.4561-0.10830.4540.2416-0.218-0.29360.0545-0.24960.1620.0974-0.0210.32840.03450.36266.9083-32.183130.5107
54.2739-0.611.47246.26970.75566.0453-0.31440.48030.3197-1.1624-0.01041.6166-0.56-0.96740.20170.37630.11410.03240.60450.07740.655462.281-31.097519.646
64.44081.3628-2.46434.2671-1.50714.0577-0.20490.4998-0.1169-0.65090.2433-0.57430.71950.06280.15310.209-0.03490.15850.57780.07340.425472.6898-34.363223.177
72.96781.8486-0.77295.50610.38840.39170.01360.02040.4644-0.06840.0173-0.3377-0.0984-0.2303-0.00070.2030.0453-0.03760.56020.0860.432361.7163-31.806626.6881
87.6103-0.40162.28440.02280.09092.13670.1714-0.9319-0.7423-0.1570.06220.02940.253-0.1064-0.18410.2904-0.04720.05480.38490.05430.415138.8219-45.77431.5949
94.4065-0.5748-1.46282.33520.09542.9810.05590.4638-0.0762-0.30490.04680.0246-0.01220.3191-0.06510.2383-0.0299-0.00730.5088-0.10690.30142.1828-44.253311.1188
103.2045-0.59311.13831.05270.25352.6259-0.00610.7587-0.2659-0.23820.03980.03610.07340.2888-0.00030.2579-0.01910.06950.3916-0.00570.38149.6915-45.895115.2967
114.07871.2933-1.24524.42770.36152.6845-0.0414-0.5876-0.46790.26180.05520.45240.33690.2878-0.11220.16760.0907-0.00630.39840.06640.4837-36.4615-56.040730.2972
120.3181-0.4458-0.93341.63760.90252.91570.30410.5881-0.09520.2009-0.08540.3792-0.2617-0.0711-0.23580.88810.39820.75481.1707-0.02881.4434-28.011-64.686117.2616
132.6625-1.62982.15499.55831.60453.1864-0.70150.72531.0068-0.63270.4577-1.1078-0.7280.48230.27830.4102-0.0367-0.00750.4242-0.06390.4715-37.9468-49.245719.3304
145.7541-0.38380.70846.67062.43694.3157-0.4079-0.1737-0.1922-0.51580.12340.9972-0.38320.15630.39750.2228-0.0150.02630.2736-0.00670.5296-43.4117-55.753624.8307
153.95073.1927-0.41425.6186-1.1421.39460.0008-0.4484-0.85550.0954-0.2459-0.13480.23630.5440.25610.24580.01520.15460.4277-0.080.3856-31.2416-56.260726.4639
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1chain 'A' and (resid 45 through 258 )A45 - 258
2X-RAY DIFFRACTION2chain 'A' and (resid 259 through 413 )A259 - 413
3X-RAY DIFFRACTION3chain 'A' and (resid 414 through 491 )A414 - 491
4X-RAY DIFFRACTION4chain 'B' and (resid 1 through 39 )B1 - 39
5X-RAY DIFFRACTION5chain 'B' and (resid 40 through 52 )B40 - 52
6X-RAY DIFFRACTION6chain 'B' and (resid 53 through 90 )B53 - 90
7X-RAY DIFFRACTION7chain 'B' and (resid 91 through 118 )B91 - 118
8X-RAY DIFFRACTION8chain 'C' and (resid 45 through 235 )C45 - 235
9X-RAY DIFFRACTION9chain 'C' and (resid 236 through 377 )C236 - 377
10X-RAY DIFFRACTION10chain 'C' and (resid 378 through 491 )C378 - 491
11X-RAY DIFFRACTION11chain 'D' and (resid 1 through 39 )D1 - 39
12X-RAY DIFFRACTION12chain 'D' and (resid 40 through 45 )D40 - 45
13X-RAY DIFFRACTION13chain 'D' and (resid 46 through 63 )D46 - 63
14X-RAY DIFFRACTION14chain 'D' and (resid 64 through 90 )D64 - 90
15X-RAY DIFFRACTION15chain 'D' and (resid 91 through 118 )D91 - 118

+
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