6GY5

Crystal structure of the kelch domain of human KLHL20 in complex with DAPK1 peptide


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.09 Å
  • R-Value Free: 0.172 
  • R-Value Work: 0.153 
  • R-Value Observed: 0.154 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Structural Basis for Recruitment of DAPK1 to the KLHL20 E3 Ligase.

Chen, Z.Picaud, S.Filippakopoulos, P.D'Angiolella, V.Bullock, A.N.

(2019) Structure 27: 1395-1404.e4

  • DOI: https://doi.org/10.1016/j.str.2019.06.005
  • Primary Citation of Related Structures:  
    6GY5

  • PubMed Abstract: 

    BTB-Kelch proteins form the largest subfamily of Cullin-RING E3 ligases, yet their substrate complexes are mapped and structurally characterized only for KEAP1 and KLHL3. KLHL20 is a related CUL3-dependent ubiquitin ligase linked to autophagy, cancer, and Alzheimer's disease that promotes the ubiquitination and degradation of substrates including DAPK1, PML, and ULK1. We identified an "LPDLV"-containing motif in the DAPK1 death domain that determines its recruitment and degradation by KLHL20. A 1.1-Å crystal structure of a KLHL20 Kelch domain-DAPK1 peptide complex reveals DAPK1 binding as a loose helical turn that inserts deeply into the central pocket of the Kelch domain to contact all six blades of the β propeller. Here, KLHL20 forms salt-bridge and hydrophobic interactions including tryptophan and cysteine residues ideally positioned for covalent inhibitor development. The structure highlights the diverse binding modes of β-propeller domains versus linear grooves and suggests a new target for structure-based drug design.


  • Organizational Affiliation

    Structural Genomics Consortium, University of Oxford, Old Road Campus, Roosevelt Drive, Oxford OX3 7DQ, UK.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Kelch-like protein 20304Homo sapiensMutation(s): 0 
Gene Names: KLHL20KLEIPKLHLX
UniProt & NIH Common Fund Data Resources
Find proteins for Q9Y2M5 (Homo sapiens)
Explore Q9Y2M5 
Go to UniProtKB:  Q9Y2M5
PHAROS:  Q9Y2M5
GTEx:  ENSG00000076321 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9Y2M5
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Death-associated protein kinase 1B [auth U]11Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P53355 (Homo sapiens)
Explore P53355 
Go to UniProtKB:  P53355
PHAROS:  P53355
GTEx:  ENSG00000196730 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP53355
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
EDO
Query on EDO

Download Ideal Coordinates CCD File 
D [auth A]
E [auth A]
F [auth A]
G [auth A]
H [auth A]
D [auth A],
E [auth A],
F [auth A],
G [auth A],
H [auth A],
I [auth A],
J [auth A],
K [auth A],
L [auth A]
1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
CL
Query on CL

Download Ideal Coordinates CCD File 
C [auth A]CHLORIDE ION
Cl
VEXZGXHMUGYJMC-UHFFFAOYSA-M
NA
Query on NA

Download Ideal Coordinates CCD File 
M [auth A]
N [auth A]
O [auth A]
P [auth A]
Q [auth A]
M [auth A],
N [auth A],
O [auth A],
P [auth A],
Q [auth A],
R [auth A],
S [auth A],
T [auth A],
U [auth A],
V [auth A],
W [auth A],
X [auth A],
Y [auth A],
Z [auth A]
SODIUM ION
Na
FKNQFGJONOIPTF-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.09 Å
  • R-Value Free: 0.172 
  • R-Value Work: 0.153 
  • R-Value Observed: 0.154 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 40.459α = 90
b = 47.361β = 90
c = 151.933γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
Aimlessdata scaling
PHASERphasing
PDB_EXTRACTdata extraction

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Wellcome TrustUnited KingdomH9R00050

Revision History  (Full details and data files)

  • Version 1.0: 2018-08-08
    Type: Initial release
  • Version 1.1: 2019-08-21
    Changes: Data collection, Database references
  • Version 1.2: 2019-09-18
    Changes: Data collection, Database references
  • Version 1.3: 2024-01-17
    Changes: Data collection, Database references, Derived calculations, Refinement description