[English] 日本語
Yorodumi
- PDB-6o3j: Crystal structure of the Fab fragment of the human HIV-1 neutrali... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6o3j
TitleCrystal structure of the Fab fragment of the human HIV-1 neutralizing antibody PGZL1 in complex with its MPER peptide epitope (region 671-683 of HIV-1 gp41) and phosphatidic acid (06:0 PA)
Components
  • MPER peptide, region 671-683 of HIV-1 gp41
  • PGZL1 heavy chain
  • PGZL1 light chain
KeywordsIMMUNE SYSTEM / PGZL1 ANTI HIV-1 / GP41 MPER / MEMBRANE LIPIDS / BROADLY NEUTRALISING HIV-1 ANTIBODY
Function / homology
Function and homology information


Synthesis and processing of ENV and VPU / evasion of host immune response / Alpha-defensins / Dectin-2 family / Binding and entry of HIV virion / positive regulation of plasma membrane raft polarization / positive regulation of receptor clustering / positive regulation of establishment of T cell polarity / virus-mediated perturbation of host defense response / host cell endosome membrane ...Synthesis and processing of ENV and VPU / evasion of host immune response / Alpha-defensins / Dectin-2 family / Binding and entry of HIV virion / positive regulation of plasma membrane raft polarization / positive regulation of receptor clustering / positive regulation of establishment of T cell polarity / virus-mediated perturbation of host defense response / host cell endosome membrane / actin filament organization / Assembly Of The HIV Virion / Budding and maturation of HIV virion / clathrin-dependent endocytosis of virus by host cell / viral protein processing / symbiont entry into host cell / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane / viral envelope / virion attachment to host cell / host cell plasma membrane / virion membrane / structural molecule activity / membrane
Similarity search - Function
Envelope glycoprotein Gp160 / Retroviral envelope protein / Retroviral envelope protein GP41-like / Gp120 core superfamily / Envelope glycoprotein GP120 / Human immunodeficiency virus 1, envelope glycoprotein Gp120 / Immunoglobulins / Immunoglobulin-like / Sandwich / Mainly Beta
Similarity search - Domain/homology
(2R)-3-(phosphonooxy)propane-1,2-diyl dihexanoate / Envelope glycoprotein gp160
Similarity search - Component
Biological speciesHomo sapiens (human)
Human immunodeficiency virus 1
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 3.416 Å
AuthorsIrimia, A. / Wilson, I.A.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)UM1 AI100663 United States
CitationJournal: Nat Commun / Year: 2019
Title: An MPER antibody neutralizes HIV-1 using germline features shared among donors.
Authors: Lei Zhang / Adriana Irimia / Lingling He / Elise Landais / Kimmo Rantalainen / Daniel P Leaman / Thomas Vollbrecht / Armando Stano / Daniel I Sands / Arthur S Kim / / Pascal Poignard / ...Authors: Lei Zhang / Adriana Irimia / Lingling He / Elise Landais / Kimmo Rantalainen / Daniel P Leaman / Thomas Vollbrecht / Armando Stano / Daniel I Sands / Arthur S Kim / / Pascal Poignard / Dennis R Burton / Ben Murrell / Andrew B Ward / Jiang Zhu / Ian A Wilson / Michael B Zwick /
Abstract: The membrane-proximal external region (MPER) of HIV-1 envelope glycoprotein (Env) can be targeted by neutralizing antibodies of exceptional breadth. MPER antibodies usually have long, hydrophobic ...The membrane-proximal external region (MPER) of HIV-1 envelope glycoprotein (Env) can be targeted by neutralizing antibodies of exceptional breadth. MPER antibodies usually have long, hydrophobic CDRH3s, lack activity as inferred germline precursors, are often from the minor IgG3 subclass, and some are polyreactive, such as 4E10. Here we describe an MPER broadly neutralizing antibody from the major IgG1 subclass, PGZL1, which shares germline V/D-region genes with 4E10, has a shorter CDRH3, and is less polyreactive. A recombinant sublineage variant pan-neutralizes a 130-isolate panel at 1.4 μg/ml (IC). Notably, a germline revertant with mature CDR3s neutralizes 12% of viruses and still binds MPER after DJ reversion. Crystal structures of lipid-bound PGZL1 variants and cryo-EM reconstruction of an Env-PGZL1 complex reveal how these antibodies recognize MPER and viral membrane. Discovery of common genetic and structural elements among MPER antibodies from different patients suggests that such antibodies could be elicited using carefully designed immunogens.
History
DepositionFeb 26, 2019Deposition site: RCSB / Processing site: RCSB
Revision 1.0Dec 4, 2019Provider: repository / Type: Initial release
Revision 1.1Dec 11, 2019Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation_author.identifier_ORCID
Revision 1.2Oct 11, 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
L: PGZL1 light chain
H: PGZL1 heavy chain
B: PGZL1 light chain
A: PGZL1 heavy chain
G: MPER peptide, region 671-683 of HIV-1 gp41
I: MPER peptide, region 671-683 of HIV-1 gp41
hetero molecules


Theoretical massNumber of molelcules
Total (without water)99,6599
Polymers98,8056
Non-polymers8553
Water0
1
L: PGZL1 light chain
H: PGZL1 heavy chain
G: MPER peptide, region 671-683 of HIV-1 gp41
hetero molecules


Theoretical massNumber of molelcules
Total (without water)49,7714
Polymers49,4023
Non-polymers3681
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area5020 Å2
ΔGint-36 kcal/mol
Surface area20430 Å2
MethodPISA
2
B: PGZL1 light chain
A: PGZL1 heavy chain
I: MPER peptide, region 671-683 of HIV-1 gp41
hetero molecules


Theoretical massNumber of molelcules
Total (without water)49,8895
Polymers49,4023
Non-polymers4872
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area4830 Å2
ΔGint-33 kcal/mol
Surface area20320 Å2
MethodPISA
Unit cell
Length a, b, c (Å)181.859, 43.931, 154.526
Angle α, β, γ (deg.)90.00, 92.49, 90.00
Int Tables number5
Space group name H-MC121

-
Components

#1: Antibody PGZL1 light chain


Mass: 23300.748 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): Expi 293F / Production host: Homo sapiens (human)
#2: Antibody PGZL1 heavy chain


Mass: 23913.920 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): Expi 293F / Production host: Homo sapiens (human)
#3: Protein/peptide MPER peptide, region 671-683 of HIV-1 gp41


Mass: 2187.582 Da / Num. of mol.: 2 / Source method: obtained synthetically / Source: (synth.) Human immunodeficiency virus 1 / References: UniProt: P04578*PLUS
#4: Chemical ChemComp-44E / (2R)-3-(phosphonooxy)propane-1,2-diyl dihexanoate


Mass: 368.360 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C15H29O8P / Comment: phospholipid*YM
#5: Chemical ChemComp-MPD / (4S)-2-METHYL-2,4-PENTANEDIOL / 2-Methyl-2,4-pentanediol


Mass: 118.174 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C6H14O2 / Comment: precipitant*YM

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 3.17 Å3/Da / Density % sol: 60.9 %
Crystal growTemperature: 293.15 K / Method: vapor diffusion, sitting drop / pH: 5.5
Details: Reservoir: 0.1 M sodium acetate pH 5.5, 12% 2-methyl-2,4-pentanediol

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SSRL / Beamline: BL9-2 / Wavelength: 0.97946 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Apr 18, 2017
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97946 Å / Relative weight: 1
ReflectionResolution: 3.416→44.1 Å / Num. obs: 15913 / % possible obs: 93.4 % / Redundancy: 4.4 % / Biso Wilson estimate: 79 Å2 / CC1/2: 0.875 / Rpim(I) all: 0.11 / Rsym value: 0.21 / Net I/σ(I): 6.6
Reflection shellResolution: 3.416→3.48 Å / Redundancy: 4.4 % / Mean I/σ(I) obs: 1.8 / Num. unique obs: 810 / CC1/2: 0.572 / Rpim(I) all: 0.466 / Rsym value: 0.887 / % possible all: 95.3

-
Processing

Software
NameVersionClassification
PHENIX(1.12_2829: ???)refinement
HKL-20002.3.10data reduction
HKL-20002.3.10data scaling
PHASER2.7.17phasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 6O3D

6o3d


Resolution: 3.416→44.097 Å / SU ML: 0.43 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 27.16
RfactorNum. reflection% reflection
Rfree0.2645 795 5 %
Rwork0.2145 --
obs0.217 15907 92.82 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å
Displacement parametersBiso mean: 79 Å2
Refinement stepCycle: LAST / Resolution: 3.416→44.097 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms6814 0 29 0 6843
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0027072
X-RAY DIFFRACTIONf_angle_d0.539650
X-RAY DIFFRACTIONf_dihedral_angle_d13.2674204
X-RAY DIFFRACTIONf_chiral_restr0.0421080
X-RAY DIFFRACTIONf_plane_restr0.0051227
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
3.4158-3.62970.33751320.28272395X-RAY DIFFRACTION90
3.6297-3.90980.31781290.25622513X-RAY DIFFRACTION94
3.9098-4.30290.33461390.21962571X-RAY DIFFRACTION96
4.3029-4.92490.25411320.18572576X-RAY DIFFRACTION95
4.9249-6.20210.21621310.19452459X-RAY DIFFRACTION91
6.2021-44.1010.21681320.20392598X-RAY DIFFRACTION92

+
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