2OT3

Crystal structure of rabex-5 VPS9 domain in complex with nucleotide free RAB21


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.243 
  • R-Value Work: 0.188 
  • R-Value Observed: 0.191 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Structural basis for Rab GTPase activation by VPS9 domain exchange factors.

Delprato, A.Lambright, D.G.

(2007) Nat Struct Mol Biol 14: 406-412

  • DOI: https://doi.org/10.1038/nsmb1232
  • Primary Citation of Related Structures:  
    2OT3

  • PubMed Abstract: 

    RABEX-5 and other exchange factors with VPS9 domains regulate endocytic trafficking through activation of the Rab family GTPases RAB5, RAB21 and RAB22. Here we report the crystal structure of the RABEX-5 catalytic core in complex with nucleotide-free RAB21, a key intermediate in the exchange reaction pathway. The structure reveals how VPS9 domain exchange factors recognize Rab GTPase substrates, accelerate GDP release and stabilize the nucleotide-free conformation. We further identify an autoinhibitory element in a predicted amphipathic helix located near the C terminus of the VPS9 domain. The autoinhibitory element overlaps with the binding site for the multivalent effector RABAPTIN-5 and potently suppresses the exchange activity of RABEX-5. Autoinhibition can be partially reversed by mutation of conserved residues on the nonpolar face of the predicted amphipathic helix or by assembly of the complex with RABAPTIN-5.


  • Organizational Affiliation

    Program in Molecular Medicine and Department of Biochemistry & Molecular Pharmacology, University of Massachusetts Medical School, Two Biotech, 373 Plantation Street, Worcester, Massachusetts 01605, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Rab5 GDP/GTP exchange factor274Homo sapiensMutation(s): 0 
Gene Names: RABGEF1RABEX5
UniProt & NIH Common Fund Data Resources
Find proteins for Q9UJ41 (Homo sapiens)
Explore Q9UJ41 
Go to UniProtKB:  Q9UJ41
GTEx:  ENSG00000154710 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9UJ41
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Ras-related protein Rab-21170Homo sapiensMutation(s): 0 
Gene Names: RAB21KIAA0118
UniProt & NIH Common Fund Data Resources
Find proteins for Q9UL25 (Homo sapiens)
Explore Q9UL25 
Go to UniProtKB:  Q9UL25
PHAROS:  Q9UL25
GTEx:  ENSG00000080371 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9UL25
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.243 
  • R-Value Work: 0.188 
  • R-Value Observed: 0.191 
  • Space Group: P 21 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 71.897α = 90
b = 113.4β = 90
c = 60.533γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
HKL-2000data collection
DENZOdata reduction
SCALEPACKdata scaling
PHASERphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2007-04-24
    Type: Initial release
  • Version 1.1: 2008-05-01
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2017-10-11
    Changes: Advisory, Data collection
  • Version 1.4: 2023-08-30
    Changes: Advisory, Data collection, Database references, Refinement description