[English] 日本語
Yorodumi
- EMDB-27640: Org 2274179-0-bound Thyrotropin Receptor -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-27640
TitleOrg 2274179-0-bound Thyrotropin Receptor
Map dataOrg 2274179-0-bound Thyrotropin Receptor
Sample
  • Complex: Human Thyrotropin receptor bound to allosteric antagonist Org 2274179-0
    • Protein or peptide: Thyrotropin receptor
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 6.65 Å
AuthorsFaust B / Cheng Y / Manglik A
Funding support United States, 2 items
OrganizationGrant numberCountry
Howard Hughes Medical Institute (HHMI) United States
National Institutes of Health/National Cancer Institute (NIH/NCI) United States
CitationJournal: Nature / Year: 2022
Title: Autoantibody mimicry of hormone action at the thyrotropin receptor.
Authors: Bryan Faust / Christian B Billesbølle / Carl-Mikael Suomivuori / Isha Singh / Kaihua Zhang / Nicholas Hoppe / Antonio F M Pinto / Jolene K Diedrich / Yagmur Muftuoglu / Mariusz W ...Authors: Bryan Faust / Christian B Billesbølle / Carl-Mikael Suomivuori / Isha Singh / Kaihua Zhang / Nicholas Hoppe / Antonio F M Pinto / Jolene K Diedrich / Yagmur Muftuoglu / Mariusz W Szkudlinski / Alan Saghatelian / Ron O Dror / Yifan Cheng / Aashish Manglik /
Abstract: Thyroid hormones are vital in metabolism, growth and development. Thyroid hormone synthesis is controlled by thyrotropin (TSH), which acts at the thyrotropin receptor (TSHR). In patients with Graves' ...Thyroid hormones are vital in metabolism, growth and development. Thyroid hormone synthesis is controlled by thyrotropin (TSH), which acts at the thyrotropin receptor (TSHR). In patients with Graves' disease, autoantibodies that activate the TSHR pathologically increase thyroid hormone activity. How autoantibodies mimic thyrotropin function remains unclear. Here we determined cryo-electron microscopy structures of active and inactive TSHR. In inactive TSHR, the extracellular domain lies close to the membrane bilayer. Thyrotropin selects an upright orientation of the extracellular domain owing to steric clashes between a conserved hormone glycan and the membrane bilayer. An activating autoantibody from a patient with Graves' disease selects a similar upright orientation of the extracellular domain. Reorientation of the extracellular domain transduces a conformational change in the seven-transmembrane-segment domain via a conserved hinge domain, a tethered peptide agonist and a phospholipid that binds within the seven-transmembrane-segment domain. Rotation of the TSHR extracellular domain relative to the membrane bilayer is sufficient for receptor activation, revealing a shared mechanism for other glycoprotein hormone receptors that may also extend to other G-protein-coupled receptors with large extracellular domains.
History
DepositionJul 16, 2022-
Header (metadata) releaseAug 24, 2022-
Map releaseAug 24, 2022-
UpdateOct 12, 2022-
Current statusOct 12, 2022Processing site: RCSB / Status: Released

-
Structure visualization

Supplemental images

emd_27640.png

Downloads & links

-
Map

FileDownload / File: emd_27640.map.gz / Format: CCP4 / Size: 91.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationOrg 2274179-0-bound Thyrotropin Receptor
Voxel sizeX=Y=Z: 0.86 Å
Density
Contour LevelBy AUTHOR: 0.185
Minimum - Maximum-0.19493994 - 0.62075603
Average (Standard dev.)0.0009782183 (±0.033788815)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions288288288
Spacing288288288
CellA=B=C: 247.68001 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Half map: Org 2274179-0-bound Thyrotropin Receptor

Fileemd_27640_half_map_1.map
AnnotationOrg 2274179-0-bound Thyrotropin Receptor
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: Org 2274179-0-bound Thyrotropin Receptor

Fileemd_27640_half_map_2.map
AnnotationOrg 2274179-0-bound Thyrotropin Receptor
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : Human Thyrotropin receptor bound to allosteric antagonist Org 227...

EntireName: Human Thyrotropin receptor bound to allosteric antagonist Org 2274179-0
Components
  • Complex: Human Thyrotropin receptor bound to allosteric antagonist Org 2274179-0
    • Protein or peptide: Thyrotropin receptor

-
Supramolecule #1: Human Thyrotropin receptor bound to allosteric antagonist Org 227...

SupramoleculeName: Human Thyrotropin receptor bound to allosteric antagonist Org 2274179-0
type: complex / Chimera: Yes / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Homo sapiens (human)
Recombinant expressionOrganism: Homo sapiens (human) / Recombinant strain: expi293

-
Macromolecule #1: Thyrotropin receptor

MacromoleculeName: Thyrotropin receptor / type: protein_or_peptide / ID: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: DYKDDDDMGC SSPPCECHQE EDFRVTCKDI QRIPSLPPST QTLKLIETHL RTIPSHAFSN LPNISRIYVS IDVTLQQLES HSFYNLSKVT HIEIRNTRNL TYIDPDALKE LPLLKFLGIF NTGLKMFPDL TKVYSTDIFF ILEITDNPYM TSIPVNAFQG LCNETLTLKL ...String:
DYKDDDDMGC SSPPCECHQE EDFRVTCKDI QRIPSLPPST QTLKLIETHL RTIPSHAFSN LPNISRIYVS IDVTLQQLES HSFYNLSKVT HIEIRNTRNL TYIDPDALKE LPLLKFLGIF NTGLKMFPDL TKVYSTDIFF ILEITDNPYM TSIPVNAFQG LCNETLTLKL YNNGFTSVQG YAFNGTKLDA VYLNKNKYLT VIDKDAFGGV YSGPSLLDVS QTSVTALPSK GLEHLKELIA RNTWTLKKLP LSLSFLHLTR ADLSYPSHCC AFKNQKKIRG ILESLMCNES SMQSLRQRKS VNGQELKNPQ EETLQAFDSH YDYTICGDSE DMVCTPKSDE FNPCEDIMGY KFLRIVVWFV SLLALLGNVF VLLILLTSHY KLNVPRFLMC NLAFADFCMG MYLLLIASVD LYTHSEYYNH AIDWQTGPGC NTAGFFTVFA SELSVYTLTV ITLERWYAIT FAMRLDRKIR LRHACAIMVG GWVCCFLLAL LPLVGISSYA KVSICLPMDT ETPLALAYIV FVLTLNIVAF VIVCCCYVKI YITVRNPQYN PGDKDTKIAK RMAVLIFTDF ICMAPISFYA LSAILNKPLI TVSNSKILLV LFYPLNSCAN PFLYAIFTKA FQRDVFILLS KFGICKRQAQ AYRGQRVPPK NSTDIQVQKV THEMRQGLHN MEDVYELIEN SHLTPKKQGQ ISEEYMQTVL

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

BufferpH: 7.5
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277.15 K / Instrument: FEI VITROBOT MARK IV

-
Electron microscopy

MicroscopeTFS KRIOS
Specialist opticsEnergy filter - Name: GIF Bioquantum / Energy filter - Slit width: 20 eV
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 60.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.2 µm / Nominal defocus min: 0.8 µm / Nominal magnification: 105000
Sample stageSpecimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

+
Image processing

Particle selectionNumber selected: 7940651
CTF correctionSoftware - Name: cryoSPARC
Final reconstructionResolution.type: BY AUTHOR / Resolution: 6.65 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 57018
Initial angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC
Final angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC

-
Atomic model buiding 1

DetailsNo modelling was performed.

+
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