[English] 日本語
Yorodumi
- PDB-7z7c: Broadly neutralizing DARPin bnD.8 in complex with the HIV-1 envel... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7z7c
TitleBroadly neutralizing DARPin bnD.8 in complex with the HIV-1 envelope variable loop 3 peptide V3 (BF520)
Components
  • Broadly neutralizing DARPin bnD.8
  • Envelope glycoprotein gp160
KeywordsDE NOVO PROTEIN / DARPin / HIV
Function / homology
Function and homology information


positive regulation of plasma membrane raft polarization / positive regulation of receptor clustering / positive regulation of establishment of T cell polarity / host cell endosome membrane / clathrin-dependent endocytosis of virus by host cell / viral protein processing / fusion of virus membrane with host plasma membrane / virus-mediated perturbation of host defense response / fusion of virus membrane with host endosome membrane / viral envelope ...positive regulation of plasma membrane raft polarization / positive regulation of receptor clustering / positive regulation of establishment of T cell polarity / host cell endosome membrane / clathrin-dependent endocytosis of virus by host cell / viral protein processing / fusion of virus membrane with host plasma membrane / virus-mediated perturbation of host defense response / fusion of virus membrane with host endosome membrane / viral envelope / virion attachment to host cell / host cell plasma membrane / structural molecule activity / virion membrane / 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
Similarity search - Domain/homology
GLYCINE / Envelope glycoprotein gp160
Similarity search - Component
Biological speciessynthetic construct (others)
Human immunodeficiency virus 1
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.22 Å
AuthorsMittl, P.R. / Gloegl, M.
Funding support Switzerland, 1items
OrganizationGrant numberCountry
Swiss National Science Foundation Switzerland
CitationJournal: Nat Struct Mol Biol / Year: 2023
Title: Trapping the HIV-1 V3 loop in a helical conformation enables broad neutralization.
Authors: Matthias Glögl / Nikolas Friedrich / Gabriele Cerutti / Thomas Lemmin / Young D Kwon / Jason Gorman / Liridona Maliqi / Peer R E Mittl / Maria C Hesselman / Daniel Schmidt / Jacqueline ...Authors: Matthias Glögl / Nikolas Friedrich / Gabriele Cerutti / Thomas Lemmin / Young D Kwon / Jason Gorman / Liridona Maliqi / Peer R E Mittl / Maria C Hesselman / Daniel Schmidt / Jacqueline Weber / Caio Foulkes / Adam S Dingens / Tatsiana Bylund / Adam S Olia / Raffaello Verardi / Thomas Reinberg / Nicolas S Baumann / Peter Rusert / Birgit Dreier / Lawrence Shapiro / Peter D Kwong / Andreas Plückthun / Alexandra Trkola /
Abstract: The third variable (V3) loop on the human immunodeficiency virus 1 (HIV-1) envelope glycoprotein trimer is indispensable for virus cell entry. Conformational masking of V3 within the trimer allows ...The third variable (V3) loop on the human immunodeficiency virus 1 (HIV-1) envelope glycoprotein trimer is indispensable for virus cell entry. Conformational masking of V3 within the trimer allows efficient neutralization via V3 only by rare, broadly neutralizing glycan-dependent antibodies targeting the closed prefusion trimer but not by abundant antibodies that access the V3 crown on open trimers after CD4 attachment. Here, we report on a distinct category of V3-specific inhibitors based on designed ankyrin repeat protein (DARPin) technology that reinstitute the CD4-bound state as a key neutralization target with up to >90% breadth. Broadly neutralizing DARPins (bnDs) bound V3 solely on open envelope and recognized a four-turn amphipathic α-helix in the carboxy-terminal half of V3 (amino acids 314-324), which we termed 'αV3C'. The bnD contact surface on αV3C was as conserved as the CD4 binding site. Molecular dynamics and escape mutation analyses underscored the functional relevance of αV3C, highlighting the potential of αV3C-based inhibitors and, more generally, of postattachment inhibition of HIV-1.
History
DepositionMar 15, 2022Deposition site: PDBE / Processing site: PDBE
Revision 1.0Mar 29, 2023Provider: repository / Type: Initial release
Revision 1.1Aug 23, 2023Group: Data collection / Database references / Category: chem_comp_atom / chem_comp_bond / citation
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.pdbx_database_id_DOI / _citation.title / _citation.year
Revision 1.2Aug 30, 2023Group: Database references / Category: citation / citation_author / Item: _citation.pdbx_database_id_PubMed / _citation.title
Revision 1.3Sep 20, 2023Group: 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 1.4Feb 7, 2024Group: Refinement description / Category: pdbx_initial_refinement_model

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Broadly neutralizing DARPin bnD.8
B: Envelope glycoprotein gp160
hetero molecules


Theoretical massNumber of molelcules
Total (without water)19,7546
Polymers19,4932
Non-polymers2614
Water2,756153
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area2040 Å2
ΔGint-8 kcal/mol
Surface area8470 Å2
MethodPISA
Unit cell
Length a, b, c (Å)96.227, 40.602, 45.631
Angle α, β, γ (deg.)90.000, 113.910, 90.000
Int Tables number5
Space group name H-MC121
Components on special symmetry positions
IDModelComponents
11A-422-

HOH

-
Components

#1: Protein Broadly neutralizing DARPin bnD.8


Mass: 17160.244 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) synthetic construct (others) / Production host: Escherichia coli (E. coli)
#2: Protein/peptide Envelope glycoprotein gp160 / Env polyprotein / HIV-1 envelope variable loop 3 peptide V3 (BF520)


Mass: 2332.635 Da / Num. of mol.: 1 / Source method: obtained synthetically / Details: HIV-1 envelope variable loop 3 peptide V3 (BF520) / Source: (synth.) Human immunodeficiency virus 1 / References: UniProt: Q9Q714
#3: Chemical ChemComp-GLY / GLYCINE


Type: peptide linking / Mass: 75.067 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C2H5NO2
#4: Chemical ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL


Mass: 62.068 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C2H6O2
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 153 / 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: 2.09 Å3/Da / Density % sol: 41.16 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop / pH: 7.4 / Details: 20% w/v PEG3350 0.18M Triammonium citrate

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X06SA / Wavelength: 1 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Dec 13, 2020
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 1.22→41.72 Å / Num. obs: 45596 / % possible obs: 95.2 % / Redundancy: 6.8 % / Biso Wilson estimate: 18.21 Å2 / CC1/2: 0.999 / Rmerge(I) obs: 0.057 / Rpim(I) all: 0.024 / Rrim(I) all: 0.061 / Net I/σ(I): 13
Reflection shellResolution: 1.22→1.27 Å / Mean I/σ(I) obs: 1.5 / Num. unique obs: 4282 / CC1/2: 0.848 / % possible all: 90

-
Processing

Software
NameVersionClassification
REFMAC5.8.0267refinement
PDB_EXTRACT3.27data extraction
XDSVERSION Jan 31, 2020data reduction
Aimlessdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 2QYJ

2qyj


Resolution: 1.22→41.72 Å / Cor.coef. Fo:Fc: 0.983 / Cor.coef. Fo:Fc free: 0.97 / SU B: 3.778 / SU ML: 0.062 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.043 / ESU R Free: 0.047 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY
RfactorNum. reflection% reflectionSelection details
Rfree0.1968 2280 5 %RANDOM
Rwork0.1474 ---
obs0.1499 43315 95.45 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso max: 135.22 Å2 / Biso mean: 28.366 Å2 / Biso min: 12.08 Å2
Baniso -1Baniso -2Baniso -3
1--1.05 Å20 Å20.43 Å2
2--4.06 Å20 Å2
3----2.44 Å2
Refinement stepCycle: final / Resolution: 1.22→41.72 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1345 0 17 153 1515
Biso mean--33.32 43.99 -
Num. residues----180
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0130.0131434
X-RAY DIFFRACTIONr_bond_other_d0.0020.0171376
X-RAY DIFFRACTIONr_angle_refined_deg1.741.621950
X-RAY DIFFRACTIONr_angle_other_deg1.5631.5913169
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.5475190
X-RAY DIFFRACTIONr_dihedral_angle_2_deg32.49325.14768
X-RAY DIFFRACTIONr_dihedral_angle_3_deg14.75715231
X-RAY DIFFRACTIONr_dihedral_angle_4_deg5.611154
X-RAY DIFFRACTIONr_chiral_restr0.090.2185
X-RAY DIFFRACTIONr_gen_planes_refined0.010.021682
X-RAY DIFFRACTIONr_gen_planes_other0.0020.02290
X-RAY DIFFRACTIONr_rigid_bond_restr5.18832810
LS refinement shellResolution: 1.222→1.254 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.492 154 -
Rwork0.59 2937 -
all-3091 -
obs--88.92 %

+
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://pdbjlvh1.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