7L2X

cryo-EM structure of RTX-bound minimal TRPV1 with NMDG at state c

  • Classification: TRANSPORT PROTEIN
  • Organism(s): Rattus norvegicus
  • Expression System: Homo sapiens
  • Mutation(s): No 
  • Membrane Protein: Yes  OPMPDBTMMemProtMD

  • Deposited: 2020-12-17 Released: 2021-09-22 
  • Deposition Author(s): Zhang, K., Julius, D., Cheng, Y.
  • Funding Organization(s): Human Frontier Science Program (HFSP), National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS), National Institutes of Health/Office of the Director, National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)

Experimental Data Snapshot

  • Method: ELECTRON MICROSCOPY
  • Resolution: 3.26 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

wwPDB Validation   3D Report Full Report


This is version 1.1 of the entry. See complete history


Literature

Structural snapshots of TRPV1 reveal mechanism of polymodal functionality.

Zhang, K.Julius, D.Cheng, Y.

(2021) Cell 184: 5138

  • DOI: 10.1016/j.cell.2021.08.012
  • Primary Citation of Related Structures:  
    7L2H, 7L2I, 7L2J, 7L2K, 7L2L, 7L2M, 7L2N, 7L2O, 7L2P, 7L2R, 7L2S, 7L2T, 7L2U, 7L2V, 7L2W, 7L2X, 7MZ5, 7MZ6, 7MZ7, 7MZ9, 7MZA, 7MZB, 7MZC, 7MZD, 7MZE

  • PubMed Abstract: 
  • Many transient receptor potential (TRP) channels respond to diverse stimuli and conditionally conduct small and large cations. Such functional plasticity is presumably enabled by a uniquely dynamic ion selectivity filter that is regulated by physiological agents ...

    Many transient receptor potential (TRP) channels respond to diverse stimuli and conditionally conduct small and large cations. Such functional plasticity is presumably enabled by a uniquely dynamic ion selectivity filter that is regulated by physiological agents. What is currently missing is a "photo series" of intermediate structural states that directly address this hypothesis and reveal specific mechanisms behind such dynamic channel regulation. Here, we exploit cryoelectron microscopy (cryo-EM) to visualize conformational transitions of the capsaicin receptor, TRPV1, as a model to understand how dynamic transitions of the selectivity filter in response to algogenic agents, including protons, vanilloid agonists, and peptide toxins, permit permeation by small and large organic cations. These structures also reveal mechanisms governing ligand binding substates, as well as allosteric coupling between key sites that are proximal to the selectivity filter and cytoplasmic gate. These insights suggest a general framework for understanding how TRP channels function as polymodal signal integrators.


    Organizational Affiliation

    Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA, USA. Electronic address: yifan.cheng@ucsf.edu.



Macromolecules
Find similar proteins by:  (by identity cutoff)  |  Structure
Entity ID: 1
MoleculeChainsSequence LengthOrganismDetailsImage
Transient receptor potential cation channel subfamily V member 1A, C [auth B], D [auth C], B [auth D]637Rattus norvegicusMutation(s): 0 
Gene Names: Trpv1Vr1Vr1l
Membrane Entity: Yes 
UniProt
Find proteins for O35433 (Rattus norvegicus)
Explore O35433 
Go to UniProtKB:  O35433
Protein Feature View
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  • Reference Sequence
Small Molecules
Experimental Data & Validation

Experimental Data

  • Method: ELECTRON MICROSCOPY
  • Resolution: 3.26 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

Structure Validation

View Full Validation Report




Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Human Frontier Science Program (HFSP)FranceLT000471/2017-L
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)United StatesR01 GM098672
National Institutes of Health/Office of the DirectorUnited StatesS10 OD021741
National Institutes of Health/Office of the DirectorUnited StatesS10 OD020054
National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)United StatesR35 NS105038

Revision History  (Full details and data files)

  • Version 1.0: 2021-09-22
    Type: Initial release
  • Version 1.1: 2021-10-13
    Changes: Database references