5OKO

Crystal structure of human SHIP2 Phosphatase-C2 double mutant F593D/L597D


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.94 Å
  • R-Value Free: 0.229 
  • R-Value Work: 0.190 
  • R-Value Observed: 0.192 

wwPDB Validation   3D Report Full Report


This is version 1.1 of the entry. See complete history


Literature

Structural basis for interdomain communication in SHIP2 providing high phosphatase activity.

Le Coq, J.Camacho-Artacho, M.Velazquez, J.V.Santiveri, C.M.Gallego, L.H.Campos-Olivas, R.Dolker, N.Lietha, D.

(2017) Elife 6

  • DOI: https://doi.org/10.7554/eLife.26640
  • Primary Citation of Related Structures:  
    5OKM, 5OKN, 5OKO, 5OKP

  • PubMed Abstract: 

    SH2-containing-inositol-5-phosphatases (SHIPs) dephosphorylate the 5-phosphate of phosphatidylinositol-3,4,5-trisphosphate (PI(3,4,5)P 3 ) and play important roles in regulating the PI3K/Akt pathway in physiology and disease. Aiming to uncover interdomain regulatory mechanisms in SHIP2, we determined crystal structures containing the 5-phosphatase and a proximal region adopting a C2 fold. This reveals an extensive interface between the two domains, which results in significant structural changes in the phosphatase domain. Both the phosphatase and C2 domains bind phosphatidylserine lipids, which likely helps to position the active site towards its substrate. Although located distant to the active site, the C2 domain greatly enhances catalytic turnover. Employing molecular dynamics, mutagenesis and cell biology, we identify two distinct allosteric signaling pathways, emanating from hydrophobic or polar interdomain interactions, differentially affecting lipid chain or headgroup moieties of PI(3,4,5)P 3 . Together, this study reveals details of multilayered C2-mediated effects important for SHIP2 activity and points towards interesting new possibilities for therapeutic interventions.


  • Organizational Affiliation

    Cell Signalling and Adhesion Group, Spanish National Cancer Research Centre, Madrid, Spain.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2
A, B
461Homo sapiensMutation(s): 2 
Gene Names: INPPL1SHIP2
EC: 3.1.3.86
UniProt & NIH Common Fund Data Resources
Find proteins for O15357 (Homo sapiens)
Explore O15357 
Go to UniProtKB:  O15357
PHAROS:  O15357
GTEx:  ENSG00000165458 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO15357
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.94 Å
  • R-Value Free: 0.229 
  • R-Value Work: 0.190 
  • R-Value Observed: 0.192 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 44.035α = 90
b = 81.118β = 92.85
c = 128.9γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
XDSdata reduction
Aimlessdata scaling
PHASERphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2017-08-23
    Type: Initial release
  • Version 1.1: 2024-05-08
    Changes: Data collection, Database references