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- PDB-8u08: Crystal structure of 10E8-GT11 scaffold in complex with a human 1... -

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Basic information

Entry
Database: PDB / ID: 8u08
TitleCrystal structure of 10E8-GT11 scaffold in complex with a human 10E8 inferred germline (10E8-iGL1)
Components
  • 10E8-GT11 epitope scaffold
  • 10E8-IGL1 heavy chain
  • 10E8-IGL1 light chain
KeywordsIMMUNE SYSTEM / Vaccine / broadly neutralizing antibody / HIV / gp41
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.98 Å
AuthorsIrimia, A. / Wilson, I.A.
Funding support United States, 2items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)AI144462 United States
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)AI147826 United States
CitationJournal: Nat Immunol / Year: 2024
Title: Vaccination induces broadly neutralizing antibody precursors to HIV gp41.
Authors: Torben Schiffner / Ivy Phung / Rashmi Ray / Adriana Irimia / Ming Tian / Olivia Swanson / Jeong Hyun Lee / Chang-Chun D Lee / Ester Marina-Zárate / So Yeon Cho / Jiachen Huang / Gabriel ...Authors: Torben Schiffner / Ivy Phung / Rashmi Ray / Adriana Irimia / Ming Tian / Olivia Swanson / Jeong Hyun Lee / Chang-Chun D Lee / Ester Marina-Zárate / So Yeon Cho / Jiachen Huang / Gabriel Ozorowski / Patrick D Skog / Andreia M Serra / Kimmo Rantalainen / Joel D Allen / Sabyasachi Baboo / Oscar L Rodriguez / Sunny Himansu / Jianfu Zhou / Jonathan Hurtado / Claudia T Flynn / Katherine McKenney / Colin Havenar-Daughton / Swati Saha / Kaitlyn Shields / Steven Schultze / Melissa L Smith / Chi-Hui Liang / Laura Toy / Simone Pecetta / Ying-Cing Lin / Jordan R Willis / Fabian Sesterhenn / Daniel W Kulp / Xiaozhen Hu / Christopher A Cottrell / Xiaoya Zhou / Jennifer Ruiz / Xuesong Wang / Usha Nair / Kathrin H Kirsch / Hwei-Ling Cheng / Jillian Davis / Oleksandr Kalyuzhniy / Alessia Liguori / Jolene K Diedrich / Julia T Ngo / Vanessa Lewis / Nicole Phelps / Ryan D Tingle / Skye Spencer / Erik Georgeson / Yumiko Adachi / Michael Kubitz / Saman Eskandarzadeh / Marc A Elsliger / Rama R Amara / Elise Landais / Bryan Briney / Dennis R Burton / Diane G Carnathan / Guido Silvestri / Corey T Watson / John R Yates / James C Paulson / Max Crispin / Gevorg Grigoryan / Andrew B Ward / Devin Sok / Frederick W Alt / Ian A Wilson / Facundo D Batista / Shane Crotty / William R Schief /
Abstract: A key barrier to the development of vaccines that induce broadly neutralizing antibodies (bnAbs) against human immunodeficiency virus (HIV) and other viruses of high antigenic diversity is the design ...A key barrier to the development of vaccines that induce broadly neutralizing antibodies (bnAbs) against human immunodeficiency virus (HIV) and other viruses of high antigenic diversity is the design of priming immunogens that induce rare bnAb-precursor B cells. The high neutralization breadth of the HIV bnAb 10E8 makes elicitation of 10E8-class bnAbs desirable; however, the recessed epitope within gp41 makes envelope trimers poor priming immunogens and requires that 10E8-class bnAbs possess a long heavy chain complementarity determining region 3 (HCDR3) with a specific binding motif. We developed germline-targeting epitope scaffolds with affinity for 10E8-class precursors and engineered nanoparticles for multivalent display. Scaffolds exhibited epitope structural mimicry and bound bnAb-precursor human naive B cells in ex vivo screens, protein nanoparticles induced bnAb-precursor responses in stringent mouse models and rhesus macaques, and mRNA-encoded nanoparticles triggered similar responses in mice. Thus, germline-targeting epitope scaffold nanoparticles can elicit rare bnAb-precursor B cells with predefined binding specificities and HCDR3 features.
History
DepositionAug 28, 2023Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jun 12, 2024Provider: repository / Type: Initial release
Revision 1.1Jun 19, 2024Group: 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 1.2Oct 9, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature / Item: _pdbx_entry_details.has_protein_modification

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
H: 10E8-IGL1 heavy chain
L: 10E8-IGL1 light chain
C: 10E8-GT11 epitope scaffold
hetero molecules


Theoretical massNumber of molelcules
Total (without water)65,6317
Polymers65,2633
Non-polymers3684
Water3,495194
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area6670 Å2
ΔGint-35 kcal/mol
Surface area26340 Å2
MethodPISA
Unit cell
Length a, b, c (Å)69.749, 73.905, 129.882
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121
Space group name HallP2ac2ab
Symmetry operation#1: x,y,z
#2: x+1/2,-y+1/2,-z
#3: -x,y+1/2,-z+1/2
#4: -x+1/2,-y,z+1/2

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Components

#1: Antibody 10E8-IGL1 heavy chain


Mass: 25013.984 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Plasmid: pHLSec / Cell line (production host): Freestyle 293F / Production host: Homo sapiens (human)
#2: Antibody 10E8-IGL1 light chain


Mass: 22554.832 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Plasmid: pHKLSec / Cell line (production host): Freestyle 293F / Production host: Homo sapiens (human)
#3: Protein 10E8-GT11 epitope scaffold


Mass: 17694.270 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Plasmid: pHLSec / Cell line (production host): Freestyle 293F / Production host: Homo sapiens (human)
#4: Chemical
ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


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


Mass: 18.015 Da / Num. of mol.: 194 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestN
Has protein modificationY

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Experimental details

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Experiment

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

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Sample preparation

CrystalDensity Matthews: 2.56 Å3/Da / Density % sol: 52.04 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop
Details: 0.095 M NaCitrate,19% 2-propanol, 5% glycerol, 19% PEG4000

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Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 23-ID-D / Wavelength: 1.0332 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Oct 15, 2019
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.0332 Å / Relative weight: 1
ReflectionResolution: 1.98→48.8 Å / Num. obs: 43220 / % possible obs: 92.1 % / Redundancy: 7.9 % / Biso Wilson estimate: 40.87 Å2 / CC1/2: 0.85 / Rpim(I) all: 0.052 / Rsym value: 0.149 / Net I/σ(I): 13
Reflection shellResolution: 1.98→2.01 Å / Redundancy: 5.6 % / Mean I/σ(I) obs: 1.2 / Num. unique obs: 1662 / CC1/2: 0.43 / Rpim(I) all: 0.412 / Rsym value: 1 / % possible all: 70.8

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Processing

Software
NameVersionClassification
PHENIX1.19.2_4158refinement
HKL-2000data reduction
HKL-2000data scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.98→48.78 Å / SU ML: 0.2772 / Cross valid method: FREE R-VALUE / σ(F): 1.36 / Phase error: 29.6816
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.2358 2143 4.97 %
Rwork0.1861 40963 -
obs0.1886 43106 91.37 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 53.48 Å2
Refinement stepCycle: LAST / Resolution: 1.98→48.78 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4581 0 24 194 4799
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00964790
X-RAY DIFFRACTIONf_angle_d1.13086533
X-RAY DIFFRACTIONf_chiral_restr0.0647726
X-RAY DIFFRACTIONf_plane_restr0.0111844
X-RAY DIFFRACTIONf_dihedral_angle_d18.0529673
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.98-2.030.3846990.31561878X-RAY DIFFRACTION64.13
2.03-2.080.34421060.29122233X-RAY DIFFRACTION75.4
2.08-2.140.32941290.27732371X-RAY DIFFRACTION80.72
2.14-2.20.31881390.2562539X-RAY DIFFRACTION85.67
2.2-2.270.34731350.2512718X-RAY DIFFRACTION92.75
2.27-2.350.3211570.25082864X-RAY DIFFRACTION96.89
2.35-2.450.30821450.24362863X-RAY DIFFRACTION96.6
2.45-2.560.30041580.24812883X-RAY DIFFRACTION97.66
2.56-2.690.29361490.23032910X-RAY DIFFRACTION97.67
2.69-2.860.31611450.21842912X-RAY DIFFRACTION97.73
2.86-3.080.25271580.21632955X-RAY DIFFRACTION98.2
3.08-3.390.27541610.18912919X-RAY DIFFRACTION98.03
3.39-3.880.20521500.16812981X-RAY DIFFRACTION97.81
3.88-4.890.17611510.13052925X-RAY DIFFRACTION96.19
4.89-48.780.18721610.15983012X-RAY DIFFRACTION94.21
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)
11.479479876940.951720264460.1223961211432.358903096393.558764862257.466579109220.3297728322630.1230720548350.0579735488506-0.9707423599110.0146808710939-0.583506205232-1.053607690760.434958725835-0.5442619746730.398772849347-0.0711501763950.09196175041290.4155072607970.05267195488230.3967276597157.04399762309-19.374109334225.6774686639
22.59548423601-0.228291963261.14910029881.544126121150.613465975464.830047549830.0293993578541-0.0484184813213-0.06371937176810.04711765953120.0476842454033-0.249743475438-0.111366856435-0.0101497752372-0.08925570061720.304134640385-0.05050082452540.04462112459160.2881233376830.01617312232520.2912696097562.9580767685-20.544940207635.0539503875
32.92590160142-1.00278251842-1.181274543895.416616567851.622060087385.54638769360.0185698483156-0.51586904864-0.1636221952760.6804166292570.172729366028-0.1132516716470.4911874560990.431265497076-0.2269675598410.321457030416-0.00133765270075-0.0312300112830.4453049509730.1063404488640.3802196291068.99033219994-25.71411506940.8869689267
41.02490129128-0.18474847527-0.7269878564960.4858334452441.035411114225.144595504860.0349967599375-0.0539480949117-0.2335927320430.08173064710070.0166016801746-0.1766231963990.01074731241410.0998936674225-0.04397693632910.373940141932-0.01743865309250.03713646114470.3096871524420.005523279112260.3880543308381.82037849012-22.849565633734.3024526151
50.259986505952-0.406435437264-0.5227881219021.215887975270.2074323510811.54100382361-0.1647096238280.482660124206-0.617512981115-0.1754534232210.0539615217740.759065083296-0.665089059533-0.139818448132-0.2614485171960.4323624772960.0949983985693-0.1420309888310.444229429364-0.1717955757040.592180186182-13.5795398976-14.9554158044-5.17094990544
62.82884334785-1.933952731.405169034951.64643123311-1.189422575452.94818000368-0.282488998265-0.2279060640820.153009455810.1482546006460.03067735809230.384733905652-0.309653734478-0.229190317750.2826199062630.321049655392-0.0203807129694-0.02425756870230.505476628482-0.2014888630870.458609931147-6.20066062335-14.49446959164.67155293853
72.50270844946-0.1221696639231.867182007832.68292604823-0.2723749421452.70287249851-0.9979301423070.7204816497920.781831807384-0.4730538545160.358116564457-0.338957771775-1.319235469980.002865473103950.7589794314550.482101840063-0.0584359968244-0.003284158396070.747916318366-0.1311615750390.579556495379-3.18009478125-11.7028721214-4.08885452693
83.281477659910.2938601348080.29247899114.45689840155-0.5217304845967.75822696290.621463487069-0.515450737967-0.822885727130.0589024891903-0.1427529377660.7824237410670.509495814472-1.1897639733-0.3865514698930.420432551697-0.128438472265-0.0478941970490.4768506640020.107345570290.411251973487-20.4794241745-29.662819294736.5690737031
94.277034787830.5152206833910.1792285651282.30568226758-0.2275217943224.917407936980.074739673550.09400272097560.0598831085411-0.153139620164-0.03935919404440.1342713973370.0858211083141-0.528816172954-0.04866834712830.3638787907610.007510168167580.05522087948070.5362686036940.05911355826440.315516918305-15.3375813718-22.291244600537.1658982572
103.575766455670.710629672722-0.3197032272762.71603626272-0.5658837888524.300982501590.227962060988-0.448820112882-0.1375022698770.1258884857480.448681582258-0.696469052916-0.1586554888620.448938650542-0.3883024716060.276957842777-0.0017322739659-0.01692124193020.451505412996-0.2111752099440.465481509807-14.1079662864-21.4663450776-0.363131827014
118.651015074951.189868490410.3674293482113.64896079998-0.8329497855988.646507849950.179284273361-0.839840784569-0.8376493239350.63294856849-0.106104046804-0.1599014203040.09372004897210.0639896385166-0.1776728458090.325596574173-0.0530349800669-0.007039551172070.4336428520350.07288996679140.55134016843-19.789823961-25.64309934688.03666585604
124.3790467388-0.3776410591572.243431225353.05442318323-2.401275151912.806875680870.3595654314941.32724765366-1.3131290296-0.734155331203-0.368606179468-0.6858843829651.200383661350.396669991868-0.3585059299380.1600351540770.0366007382111-0.09640585469750.412751188038-0.2873918856360.814984391861-10.4353877386-29.9801210651-4.68906384914
134.83943976787-0.0697225683719-0.01272723023793.542977611891.268626950396.94428037646-0.2591003612351.05470790815-0.884659798546-0.03174879424540.0705447748150.04599170968370.40749644435-0.596135323846-0.02068710422890.295671380229-0.0500879378229-0.01650863983380.553358194854-0.1315232953450.539861623927-22.437481886-27.3353643408-3.85505981963
148.85102362122-3.34802958089-1.833661983556.508346168290.4600092962443.673220676430.139571424926-0.5583270437660.730866734473-0.2118108077750.0600788689096-0.551799254477-0.8564508424680.632244266581-0.1991676143130.601915039986-0.104037028505-0.0407535030910.598764669772-0.0003107725286170.3510122909041.2732421512-6.7810749187672.9306089026
152.91953309239-2.9370780561-1.356923577246.01205569029-1.179626784832.747813851150.4888332646620.4692168649051.035957720010.519103558524-0.695417978843-0.351441612324-0.5393119212750.6941032143330.2711833286020.67243926261-0.154546338983-0.01714220683340.8089092373240.1149192174460.6273140268783.82658203322-6.8066355765364.0541505819
167.787029511640.666925396299-1.484312633613.57475496879-1.240384948172.354322650320.601944767162-0.4295610926940.9876442797420.123809537141-0.08661137354320.0172599037597-0.5198514050180.250242518207-0.4238176159480.552166942621-0.1032426503080.02730405610350.5693194702380.02765710093410.36764016585-3.48015811527-14.367202939963.9157237453
178.11566079321-3.20015247340.6187770949774.0373606076-1.858735921451.87976923635-0.486389151553-1.118426348160.2959986306710.8858821732920.3648642346710.385432078782-0.375579675138-0.2452465144150.1161954860110.646132188343-0.0462996754165-0.009319543390220.817180313135-0.02929494654660.578982960467-7.40525091394-11.805291531374.868691127
184.630543764060.449850986504-0.6802605756312.389460053041.542889147523.285541290950.0460487759324-0.2505235628420.1236308126-0.0127768185260.03097657450340.187567385316-0.255824987323-0.132866020521-0.03613600105040.478573149773-0.07030153779-0.007852472019640.4987303299110.09000164127250.333322452795-7.16324660948-17.762141312663.8550023535
191.61859812371-0.5503990694362.75293409661.187751199651.362926009729.89983306770.466562009457-1.3447439667-1.257588952470.579134572347-0.05584331891340.1600934982890.581494025538-0.953799690396-0.3579525161810.82462184896-0.212618167720.0214385725091.052262975210.2629823401910.614561106205-11.2183361751-24.573933106778.5654111794
204.37197506366-1.331888452490.3831492180413.244035510382.489133564676.94050448637-0.0589020698792-0.783660191983-0.4557497740570.7520392072980.154186310367-0.1300508550260.369056718450.148456080418-0.043252662490.606648739699-0.0920131673343-0.1166084458770.6803922982830.2289978401040.5375080274662.20518608243-26.886514281774.3093613953
214.76614104157-6.54216911044-4.179318714229.624700201334.898348381274.70090996377-0.144577273319-1.075888481260.8567918140410.867101449920.235765842836-0.9194940113350.2000370337560.102230198902-0.0009941308499340.7018770683-0.176255055403-0.04695341006121.060492286420.01101921217260.4081586715541.71965784811-15.055796749579.5715451208
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 )HA1 - 171 - 17
22chain 'H' and (resid 18 through 51 )HA18 - 5118 - 51
33chain 'H' and (resid 52 through 75 )HA52 - 7552 - 75
44chain 'H' and (resid 76 through 137 )HA76 - 13776 - 137
55chain 'H' and (resid 138 through 152 )HA138 - 152138 - 152
66chain 'H' and (resid 153 through 221 )HA153 - 221153 - 221
77chain 'H' and (resid 222 through 234 )HA222 - 234222 - 234
88chain 'L' and (resid 2 through 27 )LB2 - 271 - 26
99chain 'L' and (resid 28 through 108 )LB28 - 10827 - 107
1010chain 'L' and (resid 109 through 139 )LB109 - 139108 - 138
1111chain 'L' and (resid 140 through 175 )LB140 - 175139 - 174
1212chain 'L' and (resid 176 through 189 )LB176 - 189175 - 188
1313chain 'L' and (resid 190 through 212 )LB190 - 212189 - 211
1414chain 'C' and (resid 2 through 17 )CC2 - 171 - 16
1515chain 'C' and (resid 18 through 35 )CC18 - 3517 - 34
1616chain 'C' and (resid 36 through 60 )CC36 - 6035 - 59
1717chain 'C' and (resid 61 through 73 )CC61 - 7360 - 72
1818chain 'C' and (resid 74 through 110 )CC74 - 11073 - 109
1919chain 'C' and (resid 111 through 123 )CC111 - 123110 - 122
2020chain 'C' and (resid 124 through 147 )CC124 - 147123 - 146
2121chain 'C' and (resid 148 through 155 )CC148 - 155147 - 154

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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

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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

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