6S9R

Crystal structure of SSDP from D. melanogaster


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.4 Å
  • R-Value Free: 0.265 
  • R-Value Work: 0.225 

wwPDB Validation 3D Report Full Report


This is version 1.1 of the entry. See complete history

Literature

Rotational symmetry of the structured Chip/LDB-SSDP core module of the Wnt enhanceosome.

Renko, M.Fiedler, M.Rutherford, T.J.Schaefer, J.V.Pluckthun, A.Bienz, M.

(2019) Proc.Natl.Acad.Sci.USA 116: 20977-20983

  • DOI: 10.1073/pnas.1912705116
  • Primary Citation of Related Structures:  

  • PubMed Abstract: 
  • The Chip/LIM-domain binding protein (LDB)-single-stranded DNA-binding protein (SSDP) (ChiLS) complex controls numerous cell-fate decisions in animal cells, by mediating transcription of developmental control genes via remote enhancers. ChiLS is recru ...

    The Chip/LIM-domain binding protein (LDB)-single-stranded DNA-binding protein (SSDP) (ChiLS) complex controls numerous cell-fate decisions in animal cells, by mediating transcription of developmental control genes via remote enhancers. ChiLS is recruited to these enhancers by lineage-specific LIM-domain proteins that bind to its Chip/LDB subunit. ChiLS recently emerged as the core module of the Wnt enhanceosome, a multiprotein complex that primes developmental control genes for timely Wnt responses. ChiLS binds to NPFxD motifs within Pygopus (Pygo) and the Osa/ARID1A subunit of the BAF chromatin remodeling complex, which could synergize with LIM proteins in tethering ChiLS to enhancers. Chip/LDB and SSDP both contain N-terminal dimerization domains that constitute the bulk of their structured cores. Here, we report the crystal structures of these dimerization domains, in part aided by DARPin chaperones. We conducted systematic surface scanning by structure-designed mutations, followed by in vitro and in vivo binding assays, to determine conserved surface residues required for binding between Chip/LDB, SSDP, and Pygo-NPFxD. Based on this, and on the 4:2 (SSDP-Chip/LDB) stoichiometry of ChiLS, we derive a highly constrained structural model for this complex, which adopts a rotationally symmetrical SSDP 2 -LDB 2 -SSDP 2 architecture. Integrity of ChiLS is essential for Pygo binding, and our mutational analysis places the NPFxD pockets on either side of the Chip/LDB dimer, each flanked by an SSDP dimer. The symmetry and multivalency of ChiLS underpin its function as an enhancer module integrating Wnt signals with lineage-specific factors to operate context-dependent transcriptional switches that are pivotal for normal development and cancer.


    Organizational Affiliation

    Medical Research Council Laboratory of Molecular Biology, CB2 0QH Cambridge, United Kingdom; mb2@mrc-lmb.cam.ac.uk.,Medical Research Council Laboratory of Molecular Biology, CB2 0QH Cambridge, United Kingdom.,Department of Biochemistry, University of Zurich, 8057 Zurich, Switzerland.




Macromolecules

Find similar proteins by: Sequence  |  Structure

Entity ID: 1
MoleculeChainsSequence LengthOrganismDetails
Sequence-specific single-stranded DNA-binding protein, isoform A
A, B
89Drosophila melanogasterMutation(s): 0 
Gene Names: Ssdp (Dmel\CG7187, l(3)neo48, ssdp)
Find proteins for Q9VEB9 (Drosophila melanogaster)
Go to UniProtKB:  Q9VEB9
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.4 Å
  • R-Value Free: 0.265 
  • R-Value Work: 0.225 
  • Space Group: I 4 2 2
Unit Cell:
Length (Å)Angle (°)
a = 137.503α = 90.00
b = 137.503β = 90.00
c = 53.863γ = 90.00
Software Package:
Software NamePurpose
PDB_EXTRACTdata extraction
SHELXCDphasing
REFMACrefinement
XDSdata reduction
XSCALEdata scaling

Structure Validation

View Full Validation Report or Ramachandran Plots



Entry History & Funding Information

Deposition Data

  • Deposited Date: 2019-07-15 
  • Released Date: 2019-10-09 
  • Deposition Author(s): Renko, M., Bienz, M.

Funding OrganizationLocationGrant Number
Medical Research Council (United Kingdom)United Kingdom--

Revision History 

  • Version 1.0: 2019-10-09
    Type: Initial release
  • Version 1.1: 2019-10-23
    Type: Data collection, Database references