5VWK

Crystal structure of human Scribble PDZ1:Beta-PIX complex


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.35 Å
  • R-Value Free: 0.257 
  • R-Value Work: 0.223 
  • R-Value Observed: 0.225 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Structural basis for the differential interaction of Scribble PDZ domains with the guanine nucleotide exchange factor beta-PIX.

Lim, K.Y.B.Godde, N.J.Humbert, P.O.Kvansakul, M.

(2017) J Biol Chem 292: 20425-20436

  • DOI: https://doi.org/10.1074/jbc.M117.799452
  • Primary Citation of Related Structures:  
    5VWC, 5VWI, 5VWK

  • PubMed Abstract: 

    Scribble is a highly conserved protein regulator of cell polarity that has been demonstrated to function as a tumor suppressor or, conversely, as an oncogene in a context-dependent manner, and it also controls many physiological processes ranging from immunity to memory. Scribble consists of a leucine-rich repeat domain and four PDZ domains, with the latter being responsible for most of Scribble's complex formation with other proteins. Given the similarities of the Scribble PDZ domain sequences in their binding grooves, it is common for these domains to show overlapping preferences for the same ligand. Yet, Scribble PDZ domains can still exhibit unique binding profiles toward other ligands. This raises the fundamental question as to how these PDZ domains discriminate ligands and exert specificities in Scribble complex formation. To better understand how Scribble PDZ domains direct cell polarity signaling, we investigated here their interactions with the well-characterized Scribble binding partner β-PIX, a guanine nucleotide exchange factor. We report the interaction profiles of all isolated Scribble PDZ domains with a β-PIX peptide. We show that Scribble PDZ1 and PDZ3 are the major interactors with β-PIX and reveal a distinct binding hierarchy in the interactions between the individual Scribble PDZ domains and β-PIX. Furthermore, using crystal structures of PDZ1 and PDZ3 bound to β-PIX, we define the structural basis for Scribble's ability to specifically engage β-PIX via its PDZ domains and provide a mechanistic platform for understanding Scribble-β-PIX-coordinated cellular functions such as directional cell migration.


  • Organizational Affiliation

    From the Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria 3086.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Protein scribble homolog
A, B, C, D
122Homo sapiensMutation(s): 0 
Gene Names: SCRIBCRIB1KIAA0147LAP4SCRB1VARTUL
UniProt & NIH Common Fund Data Resources
Find proteins for Q14160 (Homo sapiens)
Explore Q14160 
Go to UniProtKB:  Q14160
PHAROS:  Q14160
GTEx:  ENSG00000180900 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ14160
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Beta-PIX
E, F, G, H
8Homo sapiensMutation(s): 0 
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
SO4
Query on SO4

Download Ideal Coordinates CCD File 
I [auth A]
J [auth A]
K [auth B]
L [auth C]
M [auth C]
I [auth A],
J [auth A],
K [auth B],
L [auth C],
M [auth C],
N [auth C],
O [auth C],
P [auth D],
Q [auth D],
R [auth D],
S [auth G],
T [auth H]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.35 Å
  • R-Value Free: 0.257 
  • R-Value Work: 0.223 
  • R-Value Observed: 0.225 
  • Space Group: P 43 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 74.76α = 90
b = 74.76β = 90
c = 222.963γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata reduction
Aimlessdata scaling
PHASERphasing

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Health and Medical Research Council (NHMRC, Australia)AustraliaAPP1007918
Australian Research Council (ARC)AustraliaFT130101349

Revision History  (Full details and data files)

  • Version 1.0: 2017-11-08
    Type: Initial release
  • Version 1.1: 2017-12-27
    Changes: Database references
  • Version 1.2: 2020-01-01
    Changes: Author supporting evidence
  • Version 1.3: 2023-10-04
    Changes: Data collection, Database references, Refinement description