4XC2

Crystal structure of GABARAP in complex with KBTBD6 LIR peptide


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.258 
  • R-Value Work: 0.198 
  • R-Value Observed: 0.201 

wwPDB Validation   3D Report Full Report


This is version 2.1 of the entry. See complete history


Literature

CUL3-KBTBD6/KBTBD7 Ubiquitin Ligase Cooperates with GABARAP Proteins to Spatially Restrict TIAM1-RAC1 Signaling.

Genau, H.M.Huber, J.Baschieri, F.Akutsu, M.Dotsch, V.Farhan, H.Rogov, V.Behrends, C.

(2015) Mol Cell 57: 995-1010

  • DOI: https://doi.org/10.1016/j.molcel.2014.12.040
  • Primary Citation of Related Structures:  
    4XC2

  • PubMed Abstract: 

    The small Rho GTPase RAC1 is an essential regulator of cellular signaling that controls actin rearrangements and cell motility. Here, we identify a novel CUL3 RING ubiquitin ligase complex, containing the substrate adaptors KBTBD6 and KBTBD7, that mediates ubiquitylation and proteasomal degradation of TIAM1, a RAC1-specific GEF. Increasing the abundance of TIAM1 by depletion of KBTBD6 and/or KBTBD7 leads to elevated RAC1 activity, changes in actin morphology, loss of focal adhesions, reduced proliferation, and enhanced invasion. KBTBD6 and KBTBD7 employ ATG8 family-interacting motifs to bind preferentially to GABARAP proteins. Surprisingly, ubiquitylation and degradation of TIAM1 by CUL3(KBTBD6/KBTBD7) depends on its binding to GABARAP proteins. Our study reveals that recruitment of CUL3(KBTBD6/KBTBD7) to GABARAP-containing vesicles regulates the abundance of membrane-associated TIAM1 and subsequently spatially restricted RAC1 signaling. Besides their role in autophagy and trafficking, we uncovered a previously unknown function of GABARAP proteins as membrane-localized signaling scaffolds.


  • Organizational Affiliation

    Institute of Biochemistry II, Goethe University School of Medicine, 60590 Frankfurt am Main, Germany.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
GABA(A) receptor-associated protein
A, B, C, D
117Homo sapiensMutation(s): 0 
Gene Names: GABARAPhCG_1987397
UniProt & NIH Common Fund Data Resources
Find proteins for O95166 (Homo sapiens)
Explore O95166 
Go to UniProtKB:  O95166
PHAROS:  O95166
GTEx:  ENSG00000170296 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO95166
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Kelch repeat and BTB domain-containing protein 6
E, F, G, H
11Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for Q86V97 (Homo sapiens)
Explore Q86V97 
Go to UniProtKB:  Q86V97
PHAROS:  Q86V97
GTEx:  ENSG00000165572 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ86V97
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.258 
  • R-Value Work: 0.198 
  • R-Value Observed: 0.201 
  • Space Group: P 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 38.893α = 65.3
b = 57.353β = 77.34
c = 67.31γ = 89.95
Software Package:
Software NamePurpose
REFMACrefinement
PDB_EXTRACTdata extraction
XDSdata reduction
SCALAdata scaling
MOLREPphasing

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
DKTKGermany--
Cluster of excellence FrankfurtGermany--
German Research FoundationGermanyBE 4685/1-1
European Research CouncilGermany282333
LOEWE Program of the State of HesseGermany--
Leibniz awardGermany--

Revision History  (Full details and data files)

  • Version 1.0: 2015-03-04
    Type: Initial release
  • Version 1.1: 2015-04-01
    Changes: Database references
  • Version 2.0: 2017-09-06
    Changes: Atomic model, Author supporting evidence
  • Version 2.1: 2024-01-10
    Changes: Data collection, Database references, Refinement description