6UQK

Cryo-EM structure of type 3 IP3 receptor revealing presence of a self-binding peptide


Experimental Data Snapshot

  • Method: ELECTRON MICROSCOPY
  • Resolution: 3.77 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

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This is version 1.3 of the entry. See complete history


Literature

Cryo-EM structure of human type-3 inositol triphosphate receptor reveals the presence of a self-binding peptide that acts as an antagonist.

Azumaya, C.M.Linton, E.A.Risener, C.J.Nakagawa, T.Karakas, E.

(2020) J Biol Chem 295: 1743-1753

  • DOI: https://doi.org/10.1074/jbc.RA119.011570
  • Primary Citation of Related Structures:  
    6UQK

  • PubMed Abstract: 

    Calcium-mediated signaling through inositol 1,4,5-triphosphate receptors (IP 3 Rs) is essential for the regulation of numerous physiological processes, including fertilization, muscle contraction, apoptosis, secretion, and synaptic plasticity. Deregulation of IP 3 Rs leads to pathological calcium signaling and is implicated in many common diseases, including cancer and neurodegenerative, autoimmune, and metabolic diseases. Revealing the mechanism of activation and inhibition of this ion channel will be critical to an improved understanding of the biological processes that are controlled by IP 3 Rs. Here, we report structural findings of the human type-3 IP 3 R (IP 3 R-3) obtained by cryo-EM (at an overall resolution of 3.8 Å), revealing an unanticipated regulatory mechanism where a loop distantly located in the primary sequence occupies the IP 3 -binding site and competitively inhibits IP 3 binding. We propose that this inhibitory mechanism must differ qualitatively among IP 3 R subtypes because of their diverse loop sequences, potentially serving as a key molecular determinant of subtype-specific calcium signaling in IP 3 Rs. In summary, our structural characterization of human IP 3 R-3 provides critical insights into the mechanistic function of IP 3 Rs and into subtype-specific regulation of these important calcium-regulatory channels.


  • Organizational Affiliation

    Department of Molecular Physiology and Biophysics, Vanderbilt University, School of Medicine, Nashville, Tennessee 37232.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
inositol 1,4,5-triphosphate receptor, type 3
A, B, C, D
2,453Homo sapiensMutation(s): 0 
Gene Names: itpr3
Membrane Entity: Yes 
UniProt & NIH Common Fund Data Resources
Find proteins for Q14573 (Homo sapiens)
Explore Q14573 
Go to UniProtKB:  Q14573
PHAROS:  Q14573
GTEx:  ENSG00000096433 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ14573
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: ELECTRON MICROSCOPY
  • Resolution: 3.77 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 
EM Software:
TaskSoftware PackageVersion
RECONSTRUCTIONcisTEM
MODEL REFINEMENTPHENIX

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Disease (NIH/NIDDK)United StatesDK020593

Revision History  (Full details and data files)

  • Version 1.0: 2020-01-15
    Type: Initial release
  • Version 1.1: 2020-01-22
    Changes: Database references
  • Version 1.2: 2020-02-19
    Changes: Database references
  • Version 1.3: 2024-03-20
    Changes: Data collection, Database references