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

+
Search query

Keywords
Author
Journal
IF

-
Structure paper

TitleArchitecture of autoinhibited and active BRAF-MEK1-14-3-3 complexes.
Journal, issue, pagesNature, Year 2019
Publish dateOct 3, 2019
AuthorsEunyoung Park / Shaun Rawson / Kunhua Li / Byeong-Won Kim / Scott B Ficarro / Gonzalo Gonzalez-Del Pino / Humayun Sharif / Jarrod A Marto / Hyesung Jeon / Michael J Eck /
PubMed AbstractRAF family kinases are RAS-activated switches that initiate signaling through the MAP kinase cascade to control cellular proliferation, differentiation and survival. RAF activity is tightly ...RAF family kinases are RAS-activated switches that initiate signaling through the MAP kinase cascade to control cellular proliferation, differentiation and survival. RAF activity is tightly regulated, and inappropriate activation is a frequent cause of cancer. At present, the structural basis of RAF regulation is poorly understood. Here we describe autoinhibited and active state structures of full-length BRAF in complexes with MEK1 and a 14-3-3 dimer, determined using cryo-electron microscopy (cryo-EM). A 4.1 Å resolution cryo-EM reconstruction reveals an inactive BRAF-MEK1 complex restrained in a cradle formed by the 14-3-3 dimer, which binds the phosphorylated S365 and S729 sites that flank the BRAF kinase domain. The BRAF cysteine-rich domain (CRD) occupies a central position that stabilizes this assembly, but the adjacent RAS-binding domain (RBD) is poorly ordered and peripheral. The 14-3-3 cradle maintains autoinhibition by sequestering the membrane-binding CRD and blocking dimerization of the BRAF kinase domain. In the active state, these inhibitory interactions are released and a single 14-3-3 dimer rearranges to bridge the C-terminal pS729 binding sites of two BRAFs, driving formation of an active, back-to-back BRAF dimer. Our structural snapshots provide a foundation for understanding normal RAF regulation and its mutational disruption in cancer and developmental syndromes.
External linksPubMed:31581174 / Publisher's page
KeywordsTRANSFERASE / Transferase/PROTEIN BINDING / Transferase-PROTEIN BINDING complex / SIGNALING PROTEIN/Transferase / SIGNALING PROTEIN-Transferase complex
MethodsEM (single particle)
Resolution4.1 - 6.8 A
Structure data

EMDB-0541:
Structure of a MAPK pathway complex

EMDB-20550:
Structure of a MAPK pathway complex

EMDB-20551:
Structure of a MAPK pathway complex

EMDB-20552:
Structure of a MAPK pathway complex

PDB-6nyb:
Structure of a MAPK pathway complex

PDB-6q0j:
Structure of a MAPK pathway complex

PDB-6q0k:
Structure of a MAPK pathway complex

PDB-6q0t:
Structure of a MAPK pathway complex

Chemicals

ChemComp-AGS:
PHOSPHOTHIOPHOSPHORIC ACID-ADENYLATE ESTER

ChemComp-ZN:
ZINC IONZinc

ChemComp-ADP:
ADENOSINE-5'-DIPHOSPHATEAdenosine diphosphate

ChemComp-MG:
MAGNESIUM IONMagnesium

ChemComp-LCJ:
5-[(2-fluoro-4-iodophenyl)amino]-N-(2-hydroxyethoxy)imidazo[1,5-a]pyridine-6-carboxamide

Source
  • homo sapiens (human)
  • Beet armyworm (beet armyworm)
  • Human (human)
  • spodoptera exigua (beet armyworm)

+
About EMN Papers

-
News

-
Jul 5, 2019. Downlodablable text data

Downlodablable text data

  • Some data of EM Navigator services can be downloaded as text file. Software such as Excel can load the data files.
    PageDataFormat
    EMN Searchsearch resultCSV, TSV, or JSON
    EMN statisticsdata tableCSV or TSV

Related info.: EMN Search / EMN Statistics

-
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

    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