[English] 日本語
Yorodumi
- PDB-6nha: Crystal structure of SYNT001, a human FcRn blocking monoclonal an... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6nha
TitleCrystal structure of SYNT001, a human FcRn blocking monoclonal antibody
Components
  • Beta-2-microglobulin
  • IgG receptor FcRn large subunit p51
  • SYNT001-Fab heavy chain
  • SYNT001-Fab light chain
KeywordsIMMUNE SYSTEM / FcRn / B2M / Circulating IgG and IgG immune complex / SYNT001
Function / homology
Function and homology information


IgG immunoglobulin transcytosis in epithelial cells mediated by FcRn immunoglobulin receptor / IgG binding / beta-2-microglobulin binding / early endosome lumen / Nef mediated downregulation of MHC class I complex cell surface expression / DAP12 interactions / Endosomal/Vacuolar pathway / Antigen Presentation: Folding, assembly and peptide loading of class I MHC / negative regulation of iron ion transport / T cell mediated cytotoxicity ...IgG immunoglobulin transcytosis in epithelial cells mediated by FcRn immunoglobulin receptor / IgG binding / beta-2-microglobulin binding / early endosome lumen / Nef mediated downregulation of MHC class I complex cell surface expression / DAP12 interactions / Endosomal/Vacuolar pathway / Antigen Presentation: Folding, assembly and peptide loading of class I MHC / negative regulation of iron ion transport / T cell mediated cytotoxicity / cellular response to iron(III) ion / negative regulation of forebrain neuron differentiation / antigen processing and presentation of exogenous protein antigen via MHC class Ib, TAP-dependent / ER to Golgi transport vesicle membrane / peptide antigen assembly with MHC class I protein complex / transferrin transport / regulation of iron ion transport / regulation of erythrocyte differentiation / negative regulation of receptor-mediated endocytosis / HFE-transferrin receptor complex / response to molecule of bacterial origin / MHC class I peptide loading complex / cellular response to iron ion / positive regulation of T cell cytokine production / antigen processing and presentation of endogenous peptide antigen via MHC class I / MHC class I protein complex / peptide antigen assembly with MHC class II protein complex / negative regulation of neurogenesis / positive regulation of receptor-mediated endocytosis / cellular response to nicotine / MHC class II protein complex / positive regulation of T cell mediated cytotoxicity / multicellular organismal-level iron ion homeostasis / specific granule lumen / peptide antigen binding / antigen processing and presentation of exogenous peptide antigen via MHC class II / phagocytic vesicle membrane / positive regulation of immune response / recycling endosome membrane / positive regulation of T cell activation / Interferon gamma signaling / Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell / negative regulation of epithelial cell proliferation / Modulation by Mtb of host immune system / sensory perception of smell / positive regulation of cellular senescence / tertiary granule lumen / DAP12 signaling / MHC class II protein complex binding / T cell differentiation in thymus / late endosome membrane / negative regulation of neuron projection development / ER-Phagosome pathway / protein refolding / early endosome membrane / amyloid fibril formation / protein homotetramerization / intracellular iron ion homeostasis / learning or memory / endosome membrane / immune response / endoplasmic reticulum lumen / Amyloid fiber formation / Golgi membrane / external side of plasma membrane / lysosomal membrane / focal adhesion / Neutrophil degranulation / SARS-CoV-2 activates/modulates innate and adaptive immune responses / structural molecule activity / endoplasmic reticulum / Golgi apparatus / protein homodimerization activity / extracellular space / extracellular exosome / extracellular region / identical protein binding / membrane / plasma membrane / cytosol
Similarity search - Function
MHC class I-like antigen recognition-like / Murine Class I Major Histocompatibility Complex, H2-DB; Chain A, domain 1 / Class I Histocompatibility antigen, domains alpha 1 and 2 / Beta-2-Microglobulin / : / MHC class I-like antigen recognition-like / MHC class I-like antigen recognition-like superfamily / MHC classes I/II-like antigen recognition protein / : / Immunoglobulin/major histocompatibility complex, conserved site ...MHC class I-like antigen recognition-like / Murine Class I Major Histocompatibility Complex, H2-DB; Chain A, domain 1 / Class I Histocompatibility antigen, domains alpha 1 and 2 / Beta-2-Microglobulin / : / MHC class I-like antigen recognition-like / MHC class I-like antigen recognition-like superfamily / MHC classes I/II-like antigen recognition protein / : / Immunoglobulin/major histocompatibility complex, conserved site / Immunoglobulins and major histocompatibility complex proteins signature. / Immunoglobulin C-Type / Immunoglobulin C1-set / Immunoglobulin C1-set domain / Ig-like domain profile. / Immunoglobulin-like domain / Immunoglobulin-like domain superfamily / Immunoglobulin-like fold / Immunoglobulins / Immunoglobulin-like / Sandwich / 2-Layer Sandwich / Mainly Beta / Alpha Beta
Similarity search - Domain/homology
IgG receptor FcRn large subunit p51 / Beta-2-microglobulin
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.381 Å
AuthorsBlumberg, R.S. / Cheung, J. / Mahmood, A. / Gandhi, A.K.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Cancer Institute (NIH/NCI) United States
CitationJournal: Sci Adv / Year: 2019
Title: Blocking FcRn in humans reduces circulating IgG levels and inhibits IgG immune complex-mediated immune responses.
Authors: Blumberg, L.J. / Humphries, J.E. / Jones, S.D. / Pearce, L.B. / Holgate, R. / Hearn, A. / Cheung, J. / Mahmood, A. / Del Tito, B. / Graydon, J.S. / Stolz, L.E. / Bitonti, A. / Purohit, S. / ...Authors: Blumberg, L.J. / Humphries, J.E. / Jones, S.D. / Pearce, L.B. / Holgate, R. / Hearn, A. / Cheung, J. / Mahmood, A. / Del Tito, B. / Graydon, J.S. / Stolz, L.E. / Bitonti, A. / Purohit, S. / de Graaf, D. / Kacena, K. / Andersen, J.T. / Christianson, G.J. / Roopenian, D.C. / Hubbard, J.J. / Gandhi, A.K. / Lasseter, K. / Pyzik, M. / Blumberg, R.S.
History
DepositionDec 21, 2018Deposition site: RCSB / Processing site: RCSB
Revision 1.0Dec 25, 2019Provider: repository / Type: Initial release
Revision 1.1Jan 15, 2020Group: 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_PubMed / _citation.title / _citation_author.identifier_ORCID / _citation_author.name
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
Revision 1.3Nov 6, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: IgG receptor FcRn large subunit p51
B: Beta-2-microglobulin
L: SYNT001-Fab light chain
H: SYNT001-Fab heavy chain
hetero molecules


Theoretical massNumber of molelcules
Total (without water)90,4047
Polymers89,7824
Non-polymers6223
Water2,990166
1
A: IgG receptor FcRn large subunit p51
B: Beta-2-microglobulin
hetero molecules

L: SYNT001-Fab light chain
H: SYNT001-Fab heavy chain
hetero molecules


Theoretical massNumber of molelcules
Total (without water)90,4047
Polymers89,7824
Non-polymers6223
Water724
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation1_565x,y+1,z1
Buried area8510 Å2
ΔGint-20 kcal/mol
Surface area36680 Å2
MethodPISA
Unit cell
Length a, b, c (Å)64.830, 77.664, 215.605
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121

-
Components

-
Protein , 2 types, 2 molecules AB

#1: Protein IgG receptor FcRn large subunit p51 / FcRn / IgG Fc fragment receptor transporter alpha chain / Neonatal Fc receptor


Mass: 31072.850 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: FCGRT, FCRN / Production host: Homo sapiens (human) / References: UniProt: P55899
#2: Protein Beta-2-microglobulin


Mass: 11748.160 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: B2M, CDABP0092, HDCMA22P / Production host: Homo sapiens (human) / References: UniProt: P61769

-
Antibody , 2 types, 2 molecules LH

#3: Antibody SYNT001-Fab light chain


Mass: 23445.938 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Production host: Cricetulus griseus (Chinese hamster)
#4: Antibody SYNT001-Fab heavy chain


Mass: 23515.377 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Production host: Cricetulus griseus (Chinese hamster)

-
Non-polymers , 2 types, 169 molecules

#5: Chemical ChemComp-NHE / 2-[N-CYCLOHEXYLAMINO]ETHANE SULFONIC ACID / N-CYCLOHEXYLTAURINE / CHES


Mass: 207.290 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C8H17NO3S / Comment: pH buffer*YM
#6: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 166 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 3.16 Å3/Da / Density % sol: 61.03 %
Crystal growTemperature: 277.15 K / Method: vapor diffusion, sitting drop / pH: 9.5 / Details: 0.1M CHES pH 9.5 50% polyethylene glycol 200

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 24-ID-E / Wavelength: 0.979 Å
DetectorType: ADSC QUANTUM 315 / Detector: CCD / Date: Nov 9, 2016
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.979 Å / Relative weight: 1
ReflectionResolution: 2.38→200 Å / Num. obs: 41525 / % possible obs: 92.5 % / Redundancy: 6.4 % / Rmerge(I) obs: 0.107 / Rpim(I) all: 0.044 / Rrim(I) all: 0.116 / Χ2: 1.009 / Net I/σ(I): 7.3
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsNum. unique obsCC1/2Rpim(I) allRrim(I) allΧ2% possible all
2.5-2.5461.81616560.4470.7771.9810.53485.5
2.54-2.596.41.43916590.5320.5921.560.55387.1
2.59-2.646.41.22416370.6490.5011.3260.56184.9
2.64-2.696.30.99216820.740.4061.0740.55886.3
2.69-2.756.40.86116450.7970.3520.9320.57685.1
2.75-2.826.30.70216450.8470.2870.760.57785.1
2.82-2.896.40.5516500.9070.2260.5960.60685.9
2.89-2.966.30.42216880.9340.1730.4570.62186.8
2.96-3.056.30.31616920.9660.1310.3430.63688.1
3.05-3.156.30.23617260.9790.0970.2560.67687.9
3.15-3.266.10.18417970.9860.0770.20.78391.9
3.26-3.396.10.14318790.9890.060.1550.85696
3.39-3.556.20.11118990.9930.0470.1210.96798.3
3.55-3.736.30.09519660.9930.040.1031.11999.5
3.73-3.976.60.08719350.9940.0360.0941.29499.6
3.97-4.276.80.07319770.9970.030.0791.509100
4.27-4.7170.06219980.9970.0250.0671.731100
4.71-5.3970.05819950.9970.0240.0631.726100
5.39-6.796.80.05820400.9970.0240.0631.559100
6.79-2006.50.04321530.9990.0180.0461.6399.4

-
Processing

Software
NameVersionClassification
PHENIXrefinement
HKL-2000data scaling
PDB_EXTRACT3.24data extraction
HKL-2000data reduction
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 3SQO, 5K59, 4N0F

3sqo

5k59

4n0f


Resolution: 2.381→49.769 Å / SU ML: 0.34 / Cross valid method: THROUGHOUT / σ(F): 1.34 / Phase error: 27.78
RfactorNum. reflection% reflection
Rfree0.2452 2013 4.85 %
Rwork0.1903 --
obs0.193 41519 93.22 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å
Displacement parametersBiso max: 142.6 Å2 / Biso mean: 60.3585 Å2 / Biso min: 24.9 Å2
Refinement stepCycle: final / Resolution: 2.381→49.769 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms6058 0 39 166 6263
Biso mean--66.94 53.6 -
Num. residues----778
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / Total num. of bins used: 14

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkNum. reflection all% reflection obs (%)
2.3812-2.44070.39141010.30962349245078
2.4407-2.50670.34731340.26382588272287
2.5067-2.58050.32691340.24552623275788
2.5805-2.66380.28311500.22472605275588
2.6638-2.7590.29241250.22772621274688
2.759-2.86940.30291220.23412705282790
2.8694-30.30671440.23042754289892
3-3.15810.26021390.22762847298695
3.1581-3.3560.31641390.21872995313499
3.356-3.6150.2641770.209730153192100
3.615-3.97870.2361630.180630073170100
3.9787-4.55410.21941460.151530793225100
4.5541-5.73630.20771540.144730823236100
5.7363-49.780.20071850.181132363421100

+
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