5XA1

Crystal structure of inositol 1,4,5-trisphosphate receptor cytosolic domain with inositol 1,4,5-trisphosphate


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 6.20 Å
  • R-Value Free: 0.382 
  • R-Value Work: 0.360 
  • R-Value Observed: 0.361 

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Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

IP3-mediated gating mechanism of the IP3 receptor revealed by mutagenesis and X-ray crystallography

Hamada, K.Miyatake, H.Terauchi, A.Mikoshiba, K.

(2017) Proc Natl Acad Sci U S A 114: 4661-4666

  • DOI: https://doi.org/10.1073/pnas.1701420114
  • Primary Citation of Related Structures:  
    5GUG, 5X9Z, 5XA0, 5XA1

  • PubMed Abstract: 

    The inositol 1,4,5-trisphosphate (IP 3 ) receptor (IP 3 R) is an IP 3 -gated ion channel that releases calcium ions (Ca 2+ ) from the endoplasmic reticulum. The IP 3 -binding sites in the large cytosolic domain are distant from the Ca 2+ conducting pore, and the allosteric mechanism of how IP 3 opens the Ca 2+ channel remains elusive. Here, we identify a long-range gating mechanism uncovered by channel mutagenesis and X-ray crystallography of the large cytosolic domain of mouse type 1 IP 3 R in the absence and presence of IP 3 Analyses of two distinct space group crystals uncovered an IP 3 -dependent global translocation of the curvature α-helical domain interfacing with the cytosolic and channel domains. Mutagenesis of the IP 3 R channel revealed an essential role of a leaflet structure in the α-helical domain. These results suggest that the curvature α-helical domain relays IP 3 -controlled global conformational dynamics to the channel through the leaflet, conferring long-range allosteric coupling from IP 3 binding to the Ca 2+ channel.


  • Organizational Affiliation

    Laboratory for Developmental Neurobiology, Brain Science Institute, RIKEN, Saitama 351-0198, Japan.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Inositol 1,4,5-trisphosphate receptor type 1
A, B
1,581Mus musculusMutation(s): 0 
Gene Names: Itpr1Insp3rPcd6Pcp1
UniProt & NIH Common Fund Data Resources
Find proteins for P11881 (Mus musculus)
Explore P11881 
Go to UniProtKB:  P11881
IMPC:  MGI:96623
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP11881
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
I3P
Query on I3P

Download Ideal Coordinates CCD File 
C [auth A],
D [auth B]
D-MYO-INOSITOL-1,4,5-TRIPHOSPHATE
C6 H15 O15 P3
MMWCIQZXVOZEGG-XJTPDSDZSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
I3P BindingDB:  5XA1 Kd: min: 0.21, max: 260 (nM) from 5 assay(s)
IC50: 300 (nM) from 1 assay(s)
EC50: min: 20, max: 209 (nM) from 7 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 6.20 Å
  • R-Value Free: 0.382 
  • R-Value Work: 0.360 
  • R-Value Observed: 0.361 
  • Space Group: P 42
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 126.803α = 90
b = 126.803β = 90
c = 367.784γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata reduction
XDSdata scaling
PHENIXphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
JSPSJapan15K06791

Revision History  (Full details and data files)

  • Version 1.0: 2017-04-19
    Type: Initial release
  • Version 1.1: 2017-05-17
    Changes: Database references
  • Version 1.2: 2023-11-22
    Changes: Data collection, Database references, Refinement description