[English] 日本語
EMN Papers
- Database of articles cited by 3DEM data entries -

+
Search query

Keywords
Author
Journal
IF

-
Structure paper

TitleCryo-EM structure of oxysterol-bound human Smoothened coupled to a heterotrimeric G.
Journal, issue, pagesNature, Year 2019
Publish dateJun 5, 2019
AuthorsXiaofeng Qi / Heng Liu / Bonne Thompson / Jeffrey McDonald / Cheng Zhang / Xiaochun Li /
PubMed AbstractThe oncoprotein Smoothened (SMO), a G-protein-coupled receptor (GPCR) of the Frizzled-class (class-F), transduces the Hedgehog signal from the tumour suppressor Patched-1 (PTCH1) to the ...The oncoprotein Smoothened (SMO), a G-protein-coupled receptor (GPCR) of the Frizzled-class (class-F), transduces the Hedgehog signal from the tumour suppressor Patched-1 (PTCH1) to the glioma-associated-oncogene (GLI) transcription factors, which activates the Hedgehog signalling pathway. It has remained unknown how PTCH1 modulates SMO, how SMO is stimulated to form a complex with heterotrimeric G proteins and whether G-protein coupling contributes to the activation of GLI proteins. Here we show that 24,25-epoxycholesterol, which we identify as an endogenous ligand of PTCH1, can stimulate Hedgehog signalling in cells and can trigger G-protein signalling via human SMO in vitro. We present a cryo-electron microscopy structure of human SMO bound to 24(S),25-epoxycholesterol and coupled to a heterotrimeric G protein. The structure reveals a ligand-binding site for 24(S),25-epoxycholesterol in the 7-transmembrane region, as well as a G-coupled activation mechanism of human SMO. Notably, the G protein presents a different arrangement from that of class-A GPCR-G complexes. Our work provides molecular insights into Hedgehog signal transduction and the activation of a class-F GPCR.
External linksPubMed:31168089 / Publisher's page
KeywordsSIGNALING PROTEIN / GPCR / Complex / Hedgehog signaling
MethodsEM (single particle)
Resolution3.84 A
Structure data

EMDB-20190:
Structure of human Smoothened-Gi complex

PDB-6ot0:
Structure of human Smoothened-Gi complex

Chemicals

ChemComp-CO1:
17-[3-(3,3-DIMETHYL-OXIRANYL)-1-METHYL-PROPYL]-10,13-DIMETHYL-2,3,4,7,8,9,10,11,12,13,14,15,16,17-TETRADECAHYDRO-1H-CYCLOPENTA[A]PHENANTHREN-3-OL

Source
  • homo sapiens (human)
  • mus musculus (house mouse)

+
About EMN Papers

-
News

-
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. (see PDBe EMDB page)
  • 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 at PDBe / Contact to PDBj

-
Feb 20, 2018. PDBj/BINDS workshop in Osaka University

PDBj/BINDS workshop in Osaka University

    +
    Oct 4, 2017. Three pioneers of this field were awarded Nobel Prize in Chemistry 2017

    Three pioneers of this field were awarded Nobel Prize in Chemistry 2017

    • Jacques Dubochet (University of Lausanne, Switzerland) is a pioneer of ice-embedding method of EM specimen (as known as cryo-EM), Most of 3DEM structures in EMDB and PDB are obtained using his method.
    • Joachim Frank (Columbia University, New York, USA) is a pioneer of single particle reconstruction, which is the most used reconstruction method for 3DEM structures in EMDB and EM entries in PDB. And also, he is a develper of Spider, which is one of the most famous software in this field, and is used for some EM Navigor data (e.g. map projection/slice images).
    • Richard Henderson (MRC Laboratory of Molecular Biology, Cambridge, UK) was determined the first biomolecule structure by EM. The first EM entry in PDB, PDB-1brd is determinedby him.

    External links: The 2017 Nobel Prize in Chemistry - Press Release

    +
    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. See below links for details.
    • 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

    +
    Jun 16, 2017. Omokage search with filter

    Omokage search with filter

    • Result of Omokage search can be filtered by keywords and the database types

    Related info.: Omokage search

    Read more

    -
    EMN Papers

    Database of articles cited by 3DEM data entries

    • Database of articles cited by 3DEM data entries in EMDB and PDB
    • Using PubMed data

    Related info.: EMDB / PDB / Q: What is the data source of EM Navigator? / EM Navigator / Yorodumi Papers / Changes in new EM Navigator and Yorodumi

    Read more