3RQE

Cerebral cavernous malformation 3 (CCM3) in complex with paxillin LD1


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Free: 0.295 
  • R-Value Work: 0.240 
  • R-Value Observed: 0.243 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Molecular Recognition of Leucine-Aspartate Repeat (LD) Motifs by the Focal Adhesion Targeting Homology Domain of Cerebral Cavernous Malformation 3 (CCM3).

Li, X.Ji, W.Zhang, R.Folta-Stogniew, E.Min, W.Boggon, T.J.

(2011) J Biol Chem 286: 26138-26147

  • DOI: https://doi.org/10.1074/jbc.M110.211250
  • Primary Citation of Related Structures:  
    3RQE, 3RQF, 3RQG

  • PubMed Abstract: 

    Cerebral cavernous malformation (CCM) is a disease that affects between 0.1 and 0.5% of the human population, with mutations in CCM3 accounting for ~ 15% of the autosomal dominant form of the disease. We recently reported that CCM3 contains an N-terminal dimerization domain (CCM3D) and a C-terminal focal adhesion targeting (FAT) homology domain. Intermolecular protein-protein interactions of CCM3 are mediated by a highly conserved surface on the FAT homology domain and are affected by CCM3 truncations in the human disease. Here we report the crystal structures of CCM3 in complex with three different leucine-aspartate repeat (LD) motifs (LD1, LD2, and LD4) from the scaffolding protein paxillin, at 2.8, 2.7, and 2.5 Å resolution. We show that CCM3 binds LD motifs using the highly conserved hydrophobic patch 1 (HP1) and that this binding is similar to the binding of focal adhesion kinase and Pyk2 FAT domains to paxillin LD motifs. We further show by surface plasmon resonance that CCM3 binds paxillin LD motifs with affinities in the micromolar range, similar to FAK family FAT domains. Finally, we show that endogenous CCM3 and paxillin co-localize in mouse cerebral pericytes. These studies provide a molecular-level framework to investigate the protein-protein interactions of CCM3.


  • Organizational Affiliation

    Department of Pharmacology, Yale University School ofMedicine, New Haven, Connecticut 06520, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Programmed cell death protein 10
A, B, C, D
214Homo sapiensMutation(s): 0 
Gene Names: PDCD10
UniProt & NIH Common Fund Data Resources
Find proteins for Q9BUL8 (Homo sapiens)
Explore Q9BUL8 
Go to UniProtKB:  Q9BUL8
PHAROS:  Q9BUL8
GTEx:  ENSG00000114209 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9BUL8
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Paxillin LD1 peptide14Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P49023 (Homo sapiens)
Explore P49023 
Go to UniProtKB:  P49023
PHAROS:  P49023
GTEx:  ENSG00000089159 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP49023
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Free: 0.295 
  • R-Value Work: 0.240 
  • R-Value Observed: 0.243 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 63.161α = 90
b = 117.989β = 90
c = 123.693γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
PHASERphasing
REFMACrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2011-06-01
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2011-08-24
    Changes: Database references
  • Version 1.3: 2023-09-13
    Changes: Data collection, Database references, Refinement description, Source and taxonomy, Structure summary