6MU1

Structure of full-length IP3R1 channel bound with Adenophostin A

  • Classification: MEMBRANE PROTEIN
  • Organism(s): Rattus norvegicus
  • Mutation(s): No 
  • Membrane Protein: Yes  OPMPDBTM

  • Deposited: 2018-10-22 Released: 2018-12-05 
  • Deposition Author(s): Serysheva, I.I., Fan, G., Baker, M.R., Wang, Z., Seryshev, A., Ludtke, S.J., Baker, M.L.
  • Funding Organization(s): National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS), National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS), National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIH/NIAMS), American Heart Association, National Science Foundation (NSF, United States)

Experimental Data Snapshot

  • Method: ELECTRON MICROSCOPY
  • Resolution: 4.10 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Cryo-EM reveals ligand induced allostery underlying InsP3R channel gating.

Fan, G.Baker, M.R.Wang, Z.Seryshev, A.B.Ludtke, S.J.Baker, M.L.Serysheva, I.I.

(2018) Cell Res 28: 1158-1170

  • DOI: https://doi.org/10.1038/s41422-018-0108-5
  • Primary Citation of Related Structures:  
    6MU1, 6MU2

  • PubMed Abstract: 

    Inositol-1,4,5-trisphosphate receptors (InsP 3 Rs) are cation channels that mobilize Ca 2+ from intracellular stores in response to a wide range of cellular stimuli. The paradigm of InsP 3 R activation is the coupled interplay between binding of InsP 3 and Ca 2+ that switches the ion conduction pathway between closed and open states to enable the passage of Ca 2+ through the channel. However, the molecular mechanism of how the receptor senses and decodes ligand-binding signals into gating motion remains unknown. Here, we present the electron cryo-microscopy structure of InsP 3 R1 from rat cerebellum determined to 4.1 Å resolution in the presence of activating concentrations of Ca 2+ and adenophostin A (AdA), a structural mimetic of InsP 3 and the most potent known agonist of the channel. Comparison with the 3.9 Å-resolution structure of InsP 3 R1 in the Apo-state, also reported herein, reveals the binding arrangement of AdA in the tetrameric channel assembly and striking ligand-induced conformational rearrangements within cytoplasmic domains coupled to the dilation of a hydrophobic constriction at the gate. Together, our results provide critical insights into the mechanistic principles by which ligand-binding allosterically gates InsP 3 R channel.


  • Organizational Affiliation

    Department of Biochemistry and Molecular Biology, Structural Biology Imaging Center, McGovern Medical School at The University of Texas Health Science Center at Houston, 6431 Fannin Street, Houston, TX, 77030, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Inositol 1,4,5-trisphosphate receptor type 1A,
B [auth C],
C [auth B],
D
2,739Rattus norvegicusMutation(s): 0 
Membrane Entity: Yes 
UniProt
Find proteins for P29994 (Rattus norvegicus)
Explore P29994 
Go to UniProtKB:  P29994
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP29994
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: ELECTRON MICROSCOPY
  • Resolution: 4.10 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 
EM Software:
TaskSoftware PackageVersion
RECONSTRUCTIONRELION1.4
MODEL REFINEMENTPHENIX

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)United StatesR01GM072804
National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)United StatesR21NS106968
National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIH/NIAMS)United StatesR21AR063255
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)United StatesR01GM080139
American Heart AssociationUnited States16GRNT2972000
National Science Foundation (NSF, United States)United StatesDBI-1356306

Revision History  (Full details and data files)

  • Version 1.0: 2018-12-05
    Type: Initial release
  • Version 1.1: 2018-12-12
    Changes: Data collection, Database references
  • Version 1.2: 2019-11-27
    Changes: Author supporting evidence