4LG4

Structural Basis for Autoactivation of Human Mst2 Kinase and Its Regulation by RASSF5


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.42 Å
  • R-Value Free: 0.231 
  • R-Value Work: 0.193 
  • R-Value Observed: 0.194 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Structural Basis for Autoactivation of Human Mst2 Kinase and Its Regulation by RASSF5.

Ni, L.Li, S.Yu, J.Min, J.Brautigam, C.A.Tomchick, D.R.Pan, D.Luo, X.

(2013) Structure 21: 1757-1768

  • DOI: https://doi.org/10.1016/j.str.2013.07.008
  • Primary Citation of Related Structures:  
    4LG4, 4LGD

  • PubMed Abstract: 

    The tumor-suppressive Hippo pathway controls tissue homeostasis through balancing cell proliferation and apoptosis. Activation of the kinases Mst1 and Mst2 (Mst1/2) is a key upstream event in this pathway and remains poorly understood. Mst1/2 and their critical regulators RASSFs contain Salvador/RASSF1A/Hippo (SARAH) domains that can homo- and heterodimerize. Here, we report the crystal structures of human Mst2 alone and bound to RASSF5. Mst2 undergoes activation through transautophosphorylation at its activation loop, which requires SARAH-mediated homodimerization. RASSF5 disrupts Mst2 homodimer and blocks Mst2 autoactivation. Binding of RASSF5 to already activated Mst2, however, does not inhibit its kinase activity. Thus, RASSF5 can act as an inhibitor or a potential positive regulator of Mst2, depending on whether it binds to Mst2 before or after activation-loop phosphorylation. We propose that these temporally sensitive functions of RASSFs enable the Hippo pathway to respond to and integrate diverse cellular signals.


  • Organizational Affiliation

    Department of Pharmacology, The University of Texas Southwestern Medical Center, 6001 Forest Park Road, Dallas, TX 75390, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Serine/threonine-protein kinase 3
A, B, C, D, E
A, B, C, D, E, F
299Homo sapiensMutation(s): 1 
Gene Names: STK3KRS1MST2
EC: 2.7.11.1
UniProt & NIH Common Fund Data Resources
Find proteins for Q13188 (Homo sapiens)
Explore Q13188 
Go to UniProtKB:  Q13188
PHAROS:  Q13188
GTEx:  ENSG00000104375 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ13188
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.42 Å
  • R-Value Free: 0.231 
  • R-Value Work: 0.193 
  • R-Value Observed: 0.194 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 227.179α = 90
b = 69.771β = 108.61
c = 148.082γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
PHENIXrefinement
PDB_EXTRACTdata extraction
HKL-3000data reduction
HKL-3000data scaling
PHASERphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2013-09-18
    Type: Initial release
  • Version 1.1: 2013-10-30
    Changes: Database references
  • Version 1.2: 2017-11-15
    Changes: Refinement description
  • Version 1.3: 2023-09-20
    Changes: Data collection, Database references, Derived calculations, Refinement description