5WBK

Crystal structure of the arabidopsis thaliana Raptor in complex with the TOS peptide of human S6K1


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.11 Å
  • R-Value Free: 0.255 
  • R-Value Work: 0.209 
  • R-Value Observed: 0.211 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Mechanisms of mTORC1 activation by RHEB and inhibition by PRAS40.

Yang, H.Jiang, X.Li, B.Yang, H.J.Miller, M.Yang, A.Dhar, A.Pavletich, N.P.

(2017) Nature 552: 368-373

  • DOI: https://doi.org/10.1038/nature25023
  • Primary Citation of Related Structures:  
    5WBH, 5WBI, 5WBJ, 5WBK, 5WBL, 5WBU, 5WBY, 6BCU, 6BCX

  • PubMed Abstract: 

    The mechanistic target of rapamycin complex 1 (mTORC1) controls cell growth and metabolism in response to nutrients, energy levels, and growth factors. It contains the atypical kinase mTOR and the RAPTOR subunit that binds to the Tor signalling sequence (TOS) motif of substrates and regulators. mTORC1 is activated by the small GTPase RHEB (Ras homologue enriched in brain) and inhibited by PRAS40. Here we present the 3.0 ångström cryo-electron microscopy structure of mTORC1 and the 3.4 ångström structure of activated RHEB-mTORC1. RHEB binds to mTOR distally from the kinase active site, yet causes a global conformational change that allosterically realigns active-site residues, accelerating catalysis. Cancer-associated hyperactivating mutations map to structural elements that maintain the inactive state, and we provide biochemical evidence that they mimic RHEB relieving auto-inhibition. We also present crystal structures of RAPTOR-TOS motif complexes that define the determinants of TOS recognition, of an mTOR FKBP12-rapamycin-binding (FRB) domain-substrate complex that establishes a second substrate-recruitment mechanism, and of a truncated mTOR-PRAS40 complex that reveals PRAS40 inhibits both substrate-recruitment sites. These findings help explain how mTORC1 selects its substrates, how its kinase activity is controlled, and how it is activated by cancer-associated mutations.


  • Organizational Affiliation

    Structural Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Regulatory-associated protein of TOR 11,287Arabidopsis thalianaMutation(s): 0 
Gene Names: RAPTOR1RAPTOR1BAt3g08850T16O11.22
UniProt
Find proteins for Q93YQ1 (Arabidopsis thaliana)
Explore Q93YQ1 
Go to UniProtKB:  Q93YQ1
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ93YQ1
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Ribosomal protein S6 kinase beta-1B [auth T]14Homo sapiensMutation(s): 0 
EC: 2.7.11.1
UniProt & NIH Common Fund Data Resources
Find proteins for P23443 (Homo sapiens)
Explore P23443 
Go to UniProtKB:  P23443
PHAROS:  P23443
GTEx:  ENSG00000108443 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP23443
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.11 Å
  • R-Value Free: 0.255 
  • R-Value Work: 0.209 
  • R-Value Observed: 0.211 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 89.1α = 90
b = 113.1β = 90
c = 152.9γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
SCALEPACKdata scaling
PDB_EXTRACTdata extraction
HKL-2000data reduction
PHASERphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2017-12-20
    Type: Initial release
  • Version 1.1: 2018-04-18
    Changes: Data collection, Database references
  • Version 1.2: 2023-10-04
    Changes: Data collection, Database references, Refinement description