6HOI

Structure of Beclin1 LIR motif bound to GABARAPL1


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.14 Å
  • R-Value Free: 0.166 
  • R-Value Work: 0.145 
  • R-Value Observed: 0.146 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Members of the autophagy class III phosphatidylinositol 3-kinase complex I interact with GABARAP and GABARAPL1 via LIR motifs.

Birgisdottir, A.B.Mouilleron, S.Bhujabal, Z.Wirth, M.Sjottem, E.Evjen, G.Zhang, W.Lee, R.O'Reilly, N.Tooze, S.A.Lamark, T.Johansen, T.

(2019) Autophagy 15: 1333-1355

  • DOI: https://doi.org/10.1080/15548627.2019.1581009
  • Primary Citation of Related Structures:  
    6HOG, 6HOH, 6HOI, 6HOJ, 6HOK, 6HOL

  • PubMed Abstract: 

    Autophagosome formation depends on a carefully orchestrated interplay between membrane-associated protein complexes. Initiation of macroautophagy/autophagy is mediated by the ULK1 (unc-51 like autophagy activating kinase 1) protein kinase complex and the autophagy-specific class III phosphatidylinositol 3-kinase complex I (PtdIns3K-C1). The latter contains PIK3C3/VPS34, PIK3R4/VPS15, BECN1/Beclin 1 and ATG14 and phosphorylates phosphatidylinositol to generate phosphatidylinositol 3-phosphate (PtdIns3P). Here, we show that PIK3C3, BECN1 and ATG14 contain functional LIR motifs and interact with the Atg8-family proteins with a preference for GABARAP and GABARAPL1. High resolution crystal structures of the functional LIR motifs of these core components of PtdIns3K-C1were obtained. Variation in hydrophobic pocket 2 (HP2) may explain the specificity for the GABARAP family. Mutation of the LIR motif in ATG14 did not prevent formation of the PtdIns3K-C1 complex, but blocked colocalization with MAP1LC3B/LC3B and impaired mitophagy. The ULK-mediated phosphorylation of S29 in ATG14 was strongly dependent on a functional LIR motif in ATG14. GABARAP-preferring LIR motifs in PIK3C3, BECN1 and ATG14 may, via coincidence detection, contribute to scaffolding of PtdIns3K-C1 on membranes for efficient autophagosome formation. Abbreviations: ATG: autophagy-related; BafA1: bafilomycin A 1 ; GABARAP: GABA type A receptor-associated protein; GABARAPL1: GABA type A receptor associated protein like 1; GFP: enhanced green fluorescent protein; KO: knockout; LDS: LIR docking site; LIR: LC3-interacting region; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; PIK3C3: phosphatidylinositol 3-kinase catalytic subunit type 3; PIK3R4: phosphoinositide-3-kinase regulatory subunit 4; PtdIns3K: phosphatidylinositol 3-kinase; PtdIns3P: phosphatidylinositol-3-phosphate; SQSTM1/p62: sequestosome 1; VPS: Vacuolar protein sorting; ULK: unc-51 like autophagy activating kinase.


  • Organizational Affiliation

    a Molecular Cancer Research Group, Department of Medical Biology , University of Tromsø -The Arctic University of Norway , Tromsø , Norway.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Gamma-aminobutyric acid receptor-associated protein-like 1
A, B
123Homo sapiensMutation(s): 0 
Gene Names: GABARAPL1GEC1
UniProt & NIH Common Fund Data Resources
Find proteins for Q9H0R8 (Homo sapiens)
Explore Q9H0R8 
Go to UniProtKB:  Q9H0R8
PHAROS:  Q9H0R8
GTEx:  ENSG00000139112 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9H0R8
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Beclin-1C [auth F],
D [auth G]
10Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for Q14457 (Homo sapiens)
Explore Q14457 
Go to UniProtKB:  Q14457
PHAROS:  Q14457
GTEx:  ENSG00000126581 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ14457
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.14 Å
  • R-Value Free: 0.166 
  • R-Value Work: 0.145 
  • R-Value Observed: 0.146 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 31.99α = 90
b = 54β = 90
c = 138.98γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
xia2data reduction
DIALSdata scaling
PHASERphasing

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Research Council of NorwayNorway214448
Research Council of NorwayNorway249884

Revision History  (Full details and data files)

  • Version 1.0: 2019-02-27
    Type: Initial release
  • Version 1.1: 2019-03-13
    Changes: Data collection, Database references
  • Version 1.2: 2019-07-10
    Changes: Data collection, Database references
  • Version 1.3: 2024-01-24
    Changes: Data collection, Database references, Refinement description