7BQF

Dimerization of SAV1 WW tandem


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.220 
  • R-Value Work: 0.196 
  • R-Value Observed: 0.198 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.1 of the entry. See complete history


Literature

A WW Tandem-Mediated Dimerization Mode of SAV1 Essential for Hippo Signaling.

Lin, Z.Xie, R.Guan, K.Zhang, M.

(2020) Cell Rep 32: 108118-108118

  • DOI: https://doi.org/10.1016/j.celrep.2020.108118
  • Primary Citation of Related Structures:  
    7BQF, 7BQG

  • PubMed Abstract: 

    The canonical mammalian Hippo pathway contains a core kinase signaling cascade requiring upstream MST to form a stable complex with SAV1 in order to phosphorylate the downstream LATS/MOB complex. Though SAV1 dimerization is essential for the trans-activation of MST, the molecular mechanism underlying SAV1 dimerization is unclear. Here, we discover that the SAV1 WW tandem containing a short Pro-rich extension immediately following the WW tandem (termed as "WW12ex") forms a highly stable homodimer. The crystal structure of SAV1 WW12ex reveals that the Pro-rich extension of one subunit binds to both WW domains from the other subunit. Thus, SAV1 WW12ex forms a domain-swapped dimer instead of a WW2 homodimerization-mediated dimer. The WW12ex-mediated dimerization of SAV1 is required for the MST/SAV1 complex assembly and MST kinase activation. Finally, we show that several cancer-related SAV1 variants disrupt SAV1 dimer formation, and thus, these mutations may impair the tumor-suppression activity of SAV1.


  • Organizational Affiliation

    Division of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Protein salvador homolog 192Mus musculusMutation(s): 0 
Gene Names: Sav1Ww45Wwp3
UniProt
Find proteins for Q8VEB2 (Mus musculus)
Explore Q8VEB2 
Go to UniProtKB:  Q8VEB2
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ8VEB2
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
DIO (Subject of Investigation/LOI)
Query on DIO

Download Ideal Coordinates CCD File 
B [auth A]1,4-DIETHYLENE DIOXIDE
C4 H8 O2
RYHBNJHYFVUHQT-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.220 
  • R-Value Work: 0.196 
  • R-Value Observed: 0.198 
  • Space Group: P 31 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 46.715α = 90
b = 46.715β = 90
c = 83.151γ = 120
Software Package:
Software NamePurpose
PHENIXrefinement
HKL-3000data scaling
PHASERphasing
HKL-3000data reduction

Structure Validation

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Ligand Structure Quality Assessment 


Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
The University Grants Committee, Research Grants Council (RGC)Hong Kong--

Revision History  (Full details and data files)

  • Version 1.0: 2020-09-23
    Type: Initial release
  • Version 1.1: 2023-11-29
    Changes: Data collection, Database references, Refinement description