4GZU

Crystal structure of the DH-PH-PH domain of FARP2


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.20 Å
  • R-Value Free: 0.278 
  • R-Value Work: 0.232 
  • R-Value Observed: 0.235 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Structural Basis for Autoinhibition of the Guanine Nucleotide Exchange Factor FARP2.

He, X.Kuo, Y.C.Rosche, T.J.Zhang, X.

(2013) Structure 21: 355-364

  • DOI: https://doi.org/10.1016/j.str.2013.01.001
  • Primary Citation of Related Structures:  
    4GYV, 4GZU, 4H6Y

  • PubMed Abstract: 

    FARP2 is a Dbl-family guanine nucleotide exchange factor (GEF) that contains a 4.1, ezrin, radixin and moesin (FERM) domain, a Dbl-homology (DH) domain and two pleckstrin homology (PH) domains. FARP2 activates Rac1 or Cdc42 in response to upstream signals, thereby regulating processes such as neuronal axon guidance and bone homeostasis. How the GEF activity of FARP2 is regulated remained poorly understood. We have determined the crystal structures of the catalytic DH domain and the DH-PH-PH domains of FARP2. The structures reveal an auto-inhibited conformation in which the GEF substrate-binding site is blocked collectively by the last helix in the DH domain and the two PH domains. This conformation is stabilized by multiple interactions among the domains and two well-structured inter-domain linkers. Our cell-based activity assays confirm the suppression of the FARP2 GEF activity by these auto-inhibitory elements.


  • Organizational Affiliation

    Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75063, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
FERM, RhoGEF and pleckstrin domain-containing protein 2
A, B
501Mus musculusMutation(s): 0 
Gene Names: Farp2Kiaa0793
UniProt & NIH Common Fund Data Resources
Find proteins for Q91VS8 (Mus musculus)
Explore Q91VS8 
Go to UniProtKB:  Q91VS8
IMPC:  MGI:2385126
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ91VS8
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.20 Å
  • R-Value Free: 0.278 
  • R-Value Work: 0.232 
  • R-Value Observed: 0.235 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 184.394α = 90
b = 85.248β = 118.76
c = 103.451γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
PHENIXrefinement
PDB_EXTRACTdata extraction
HKL-3000data collection
PHENIXphasing

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2013-03-13
    Type: Initial release
  • Version 1.1: 2013-03-27
    Changes: Database references
  • Version 1.2: 2016-12-21
    Changes: Structure summary
  • Version 1.3: 2017-11-15
    Changes: Refinement description
  • Version 1.4: 2023-09-13
    Changes: Data collection, Database references, Refinement description