6MTV

Crystal structure of human Scribble PDZ1:MCC complex


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.266 
  • R-Value Work: 0.248 
  • R-Value Observed: 0.249 

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This is version 1.3 of the entry. See complete history


Literature

Structural analysis of phosphorylation-associated interactions of human MCC with Scribble PDZ domains.

Caria, S.Stewart, B.Z.Jin, R.Smith, B.J.Humbert, P.O.Kvansakul, M.

(2019) FEBS J 286: 4910-4925

  • DOI: https://doi.org/10.1111/febs.15002
  • Primary Citation of Related Structures:  
    6MTU, 6MTV

  • PubMed Abstract: 

    Scribble is a crucial adaptor protein that plays a pivotal role during establishment and control of cell polarity, impacting many physiological processes ranging from cell migration to immunity and organization of tissue architecture. Scribble harbours a leucine-rich repeat domain and four PDZ domains that mediate most of Scribble's interactions with other proteins. It has become increasingly clear that post-translational modifications substantially impact Scribble-ligand interactions, with phosphorylation being a major modulator of binding to Scribble. To better understand how Scribble PDZ domains direct cell polarity signalling and how phosphorylation impacts this process, we investigated human Scribble interactions with MCC (Mutated in Colorectal Cancer). We systematically evaluated the ability of all four individual Scribble PDZ domains to bind the PDZ-binding motif (PBM) of MCC as well as MCC phosphorylated at the -1 Ser position. We show that Scribble PDZ1 and PDZ3 are the major interactors with MCC, and that modifications to Ser at the -1 position in the MCC PBM only has a minor effect on binding to Scribble PDZ domains. We then examined the structural basis for these observations by determining the crystal structures of Scribble PDZ1 domain bound to both the unphosphorylated MCC PBM as well as phosphorylated MCC. Our structures indicated that phospho-Ser at the -1 position in MCC is not involved in major contacts with Scribble PDZ1, and in conjunction with our affinity measurements suggest that the impact of phosphorylation at the -1 position of MCC must extend beyond a simple modulation of the affinity for Scribble PDZ domains.


  • Organizational Affiliation

    Department of Biochemistry & Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria, Australia.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Protein scribble homolog
A, B
118Homo 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
Colorectal mutant cancer proteinC [auth D],
D [auth E]
8Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P23508 (Homo sapiens)
Explore P23508 
Go to UniProtKB:  P23508
PHAROS:  P23508
GTEx:  ENSG00000171444 
Entity Groups  
UniProt GroupP23508
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.266 
  • R-Value Work: 0.248 
  • R-Value Observed: 0.249 
  • Space Group: I 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 57.403α = 90
b = 55.559β = 116.12
c = 61.775γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
xia2data reduction
Aimlessdata scaling
PHASERphasing

Structure Validation

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Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Health and Medical Research Council (NHMRC, Australia)AustraliaAPP1103871
Australian Research Council (ARC)AustraliaFT130101349

Revision History  (Full details and data files)

  • Version 1.0: 2019-08-14
    Type: Initial release
  • Version 1.1: 2020-01-01
    Changes: Author supporting evidence, Database references
  • Version 1.2: 2020-01-29
    Changes: Derived calculations
  • Version 1.3: 2023-10-11
    Changes: Data collection, Database references, Refinement description