[English] 日本語
Yorodumi
- PDB-8u03: Crystal structure of non-glycosylated 10E8-GT10.1 scaffold in com... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8u03
TitleCrystal structure of non-glycosylated 10E8-GT10.1 scaffold in complex with a human 10E8 NGS precursor (10E8-NGS-03)
Components
  • (10E8-NGS-03 Fab ...) x 2
  • 10E8-GT10.1 epitope scaffold
KeywordsIMMUNE SYSTEM / Vaccine / broadly neutralizing antibody / HIV / gp41
Function / homologyIMIDAZOLE
Function and homology information
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.72 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 16, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature / Item: _pdbx_entry_details.has_protein_modification

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
H: 10E8-NGS-03 Fab heavy chain
L: 10E8-NGS-03 Fab Light Chain
C: 10E8-GT10.1 epitope scaffold
hetero molecules


Theoretical massNumber of molelcules
Total (without water)65,8185
Polymers65,5103
Non-polymers3072
Water1086
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area7070 Å2
ΔGint-28 kcal/mol
Surface area26020 Å2
MethodPISA
Unit cell
Length a, b, c (Å)69.599, 85.218, 175.432
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,y+1/2,-z

-
Components

-
Protein , 1 types, 1 molecules C

#3: Protein 10E8-GT10.1 epitope scaffold


Mass: 17870.574 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)

-
Antibody , 2 types, 2 molecules HL

#1: Antibody 10E8-NGS-03 Fab heavy chain


Mass: 25085.016 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-NGS-03 Fab 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: pHLSec / Cell line (production host): Freestyle 293F / Production host: Homo sapiens (human)

-
Non-polymers , 3 types, 8 molecules

#4: Chemical ChemComp-1PE / PENTAETHYLENE GLYCOL / PEG400


Mass: 238.278 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Formula: C10H22O6 / Comment: precipitant*YM
#5: Chemical ChemComp-IMD / IMIDAZOLE


Mass: 69.085 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C3H5N2
#6: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 6 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has ligand of interestN
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 3.97 Å3/Da / Density % sol: 69.02 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop / Details: 0.1 M Imidazole pH 8, 40% Peg400

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SSRL / Beamline: BL12-2 / Wavelength: 0.97946 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Dec 6, 2018
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97946 Å / Relative weight: 1
ReflectionResolution: 2.72→34.4 Å / Num. obs: 27880 / % possible obs: 96.2 % / Redundancy: 6 % / Biso Wilson estimate: 86.27 Å2 / CC1/2: 0.97 / Rpim(I) all: 0.037 / Rsym value: 0.086 / Net I/σ(I): 19.4
Reflection shellResolution: 2.72→2.76 Å / Redundancy: 4.2 % / Mean I/σ(I) obs: 1.2 / Num. unique obs: 1065 / CC1/2: 0.57 / Rpim(I) all: 0.53 / Rsym value: 1 / % possible all: 73.8

-
Processing

Software
NameVersionClassification
PHENIX1.19.2_4158refinement
HKL-2000data reduction
HKL-2000data scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.72→34.4 Å / SU ML: 0.505 / Cross valid method: FREE R-VALUE / σ(F): 1.35 / Phase error: 33.1939
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.2487 1389 5 %
Rwork0.2197 26404 -
obs0.2212 27793 96.1 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 106.92 Å2
Refinement stepCycle: LAST / Resolution: 2.72→34.4 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4606 0 21 6 4633
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0024760
X-RAY DIFFRACTIONf_angle_d0.53296478
X-RAY DIFFRACTIONf_chiral_restr0.0429719
X-RAY DIFFRACTIONf_plane_restr0.004829
X-RAY DIFFRACTIONf_dihedral_angle_d16.85941715
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.72-2.810.48981090.37732056X-RAY DIFFRACTION75.67
2.81-2.930.42361270.34042417X-RAY DIFFRACTION89.86
2.93-3.060.39371400.34622670X-RAY DIFFRACTION98.53
3.06-3.220.34191410.30312700X-RAY DIFFRACTION99.93
3.22-3.420.32241420.25422700X-RAY DIFFRACTION99.37
3.42-3.690.31721450.24612739X-RAY DIFFRACTION99.72
3.69-4.060.22931430.20122719X-RAY DIFFRACTION99.9
4.06-4.640.19421440.16552747X-RAY DIFFRACTION99.55
4.64-5.840.20671460.18752778X-RAY DIFFRACTION99.39
5.84-34.40.22261520.21832878X-RAY DIFFRACTION98.7
Refinement TLS params.Method: refined / Origin x: 23.6435588965 Å / Origin y: 16.9496267824 Å / Origin z: 29.9389656881 Å
111213212223313233
T0.691385529863 Å20.0326844809719 Å2-0.0206855652842 Å2-0.678198726553 Å20.0337243847438 Å2--0.780947490551 Å2
L0.531815740762 °20.381136409429 °20.272009308327 °2-0.382462460896 °20.375304958582 °2--1.28758676452 °2
S0.0890372874011 Å °0.251464006164 Å °0.0167349222937 Å °0.0523556007206 Å °-0.129633361983 Å °-0.0429685920509 Å °0.085772670797 Å °-0.230330640193 Å °-0.00156511257872 Å °
Refinement TLS groupSelection details: all

+
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