6BU0

Crystal structure of the PI3KC2alpha C2 domain in complex with IP6


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.43 Å
  • R-Value Free: 0.250 
  • R-Value Work: 0.209 
  • R-Value Observed: 0.211 

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Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Molecular Basis for Membrane Recruitment by the PX and C2 Domains of Class II Phosphoinositide 3-Kinase-C2 alpha.

Chen, K.E.Tillu, V.A.Chandra, M.Collins, B.M.

(2018) Structure 26: 1612

  • DOI: https://doi.org/10.1016/j.str.2018.08.010
  • Primary Citation of Related Structures:  
    6BTY, 6BTZ, 6BU0, 6BUB

  • PubMed Abstract: 

    Phosphorylation of phosphoinositides by the class II phosphatidylinositol 3-kinase (PI3K) PI3K-C2α is essential for many processes, including neuroexocytosis and formation of clathrin-coated vesicles. A defining feature of the class II PI3Ks is a C-terminal module composed of phox-homology (PX) and C2 membrane interacting domains; however, the mechanisms that control their specific cellular localization remain poorly understood. Here we report the crystal structure of the C2 domain of PI3K-C2α in complex with the phosphoinositide head-group mimic inositol hexaphosphate, revealing two distinct pockets for membrane binding. The C2 domain preferentially binds to phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol (3,4,5)-trisphosphate, and low-resolution structures of the combined PX-C2 module by small-angle X-ray scattering reveal a compact conformation in which cooperative lipid binding by each domain binding can occur. Finally, we demonstrate an unexpected role for calcium in perturbing the membrane interactions of the PX-C2 module, which we speculate may be important for regulating the activity of PI3K-C2α.


  • Organizational Affiliation

    Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD 4072, Australia.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit alpha
A, B, C
131Homo sapiensMutation(s): 1 
Gene Names: PIK3C2A
EC: 2.7.1.154
UniProt & NIH Common Fund Data Resources
Find proteins for O00443 (Homo sapiens)
Explore O00443 
Go to UniProtKB:  O00443
PHAROS:  O00443
GTEx:  ENSG00000011405 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO00443
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
IHP
Query on IHP

Download Ideal Coordinates CCD File 
H [auth B],
I [auth B],
K [auth C],
L [auth C]
INOSITOL HEXAKISPHOSPHATE
C6 H18 O24 P6
IMQLKJBTEOYOSI-GPIVLXJGSA-N
O4B
Query on O4B

Download Ideal Coordinates CCD File 
M [auth C]1,4,7,10,13,16-HEXAOXACYCLOOCTADECANE
C12 H24 O6
XEZNGIUYQVAUSS-UHFFFAOYSA-N
FMT
Query on FMT

Download Ideal Coordinates CCD File 
D [auth A],
E [auth A],
F [auth A],
G [auth A],
J [auth B]
FORMIC ACID
C H2 O2
BDAGIHXWWSANSR-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.43 Å
  • R-Value Free: 0.250 
  • R-Value Work: 0.209 
  • R-Value Observed: 0.211 
  • Space Group: P 21 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 91.652α = 90
b = 126.715β = 90
c = 38.655γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata reduction
Aimlessdata scaling
PHASERphasing
PDB_EXTRACTdata extraction

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2018-10-17
    Type: Initial release
  • Version 1.1: 2018-12-19
    Changes: Data collection, Database references
  • Version 1.2: 2020-10-14
    Changes: Structure summary
  • Version 1.3: 2023-10-04
    Changes: Advisory, Data collection, Database references, Refinement description