6DJR

Full-length human TRPC3 in GDN


Experimental Data Snapshot

  • Method: ELECTRON MICROSCOPY
  • Resolution: 5.80 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

wwPDB Validation   3D Report Full Report


This is version 1.5 of the entry. See complete history


Literature

Structure-function analyses of the ion channel TRPC3 reveal that its cytoplasmic domain allosterically modulates channel gating.

Sierra-Valdez, F.Azumaya, C.M.Romero, L.O.Nakagawa, T.Cordero-Morales, J.F.

(2018) J Biol Chem 293: 16102-16114

  • DOI: https://doi.org/10.1074/jbc.RA118.005066
  • Primary Citation of Related Structures:  
    6D7L, 6DJR, 6DJS

  • PubMed Abstract: 

    The transient receptor potential ion channels support Ca 2+ permeation in many organs, including the heart, brain, and kidney. Genetic mutations in transient receptor potential cation channel subfamily C member 3 (TRPC3) are associated with neurodegenerative diseases, memory loss, and hypertension. To better understand the conformational changes that regulate TRPC3 function, we solved the cryo-EM structures for the full-length human TRPC3 and its cytoplasmic domain (CPD) in the apo state at 5.8- and 4.0-Å resolution, respectively. These structures revealed that the TRPC3 transmembrane domain resembles those of other TRP channels and that the CPD is a stable module involved in channel assembly and gating. We observed the presence of a C-terminal domain swap at the center of the CPD where horizontal helices (HHs) transition into a coiled-coil bundle. Comparison of TRPC3 structures revealed that the HHs can reside in two distinct positions. Electrophysiological analyses disclosed that shortening the length of the C-terminal loop connecting the HH with the TRP helices increases TRPC3 activity and that elongating the length of the loop has the opposite effect. Our findings indicate that the C-terminal loop affects channel gating by altering the allosteric coupling between the cytoplasmic and transmembrane domains. We propose that molecules that target the HH may represent a promising strategy for controlling TRPC3-associated neurological disorders and hypertension.


  • Organizational Affiliation

    From the Department of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee 38163 and.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Transient Receptor Potential Cation Channel Subfamily C Member 3
A, B, C, D
490Homo sapiensMutation(s): 0 
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: ELECTRON MICROSCOPY
  • Resolution: 5.80 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 
EM Software:
TaskSoftware PackageVersion
MODEL REFINEMENTPHENIX1.13-2998
RECONSTRUCTIONRELION2.1

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health & Human Development (NIH/NICHD)United StatesR01HD061543
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)United StatesR01GM125629

Revision History  (Full details and data files)

  • Version 1.0: 2018-08-29
    Type: Initial release
  • Version 1.1: 2018-09-05
    Changes: Data collection, Database references
  • Version 1.2: 2018-10-24
    Changes: Data collection, Database references
  • Version 1.3: 2019-12-11
    Changes: Author supporting evidence
  • Version 1.4: 2019-12-18
    Changes: Other
  • Version 1.5: 2024-03-13
    Changes: Database references