Article

Structure of the TRPV1 ion channel determined by electron cryo-microscopy

  • Nature volume 504, pages 107112 (05 December 2013)
  • doi:10.1038/nature12822
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Abstract

Transient receptor potential (TRP) channels are sensors for a wide range of cellular and environmental signals, but elucidating how these channels respond to physical and chemical stimuli has been hampered by a lack of detailed structural information. Here we exploit advances in electron cryo-microscopy to determine the structure of a mammalian TRP channel, TRPV1, at 3.4 Å resolution, breaking the side-chain resolution barrier for membrane proteins without crystallization. Like voltage-gated channels, TRPV1 exhibits four-fold symmetry around a central ion pathway formed by transmembrane segments 5–6 (S5–S6) and the intervening pore loop, which is flanked by S1–S4 voltage-sensor-like domains. TRPV1 has a wide extracellular ‘mouth’ with a short selectivity filter. The conserved ‘TRP domain’ interacts with the S4–S5 linker, consistent with its contribution to allosteric modulation. Subunit organization is facilitated by interactions among cytoplasmic domains, including amino-terminal ankyrin repeats. These observations provide a structural blueprint for understanding unique aspects of TRP channel function.

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Accessions

Electron Microscopy Data Bank

Protein Data Bank

Data deposits

3D cryo-EM density map of TRPV1 complexes without low-pass filter and amplitude modification have been deposited in the Electron Microscopy Data Bank under the accession number EMD-5778 (TRPV1). Particle images related to this entry are available for download at http://www.ebi.ac.uk/~ardan/aspera/em-aspera-demo.html with identification no. 10005. The coordinates of atomic model of TRPV1 have been deposited in the Protein Data Bank under the accession number 3J5P.

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Acknowledgements

We thank X. Li for assistance with data acquisition using TF30 Polara and K2 Summit camera, S. Zhou and D. King for help with protein microsequencing and J.P Armache, C. Bohlen, J. Cordero-Morales and J. Osteen for discussion and reading of the manuscript. This work was supported by grants from the National Institutes of Health (R01GM098672 and S10RR026814 to Y.C. and R01NS065071 and R01NS047723 to D.J.), the National Science Foundation (DBI-0960271 to D. Agard and Y.C.) and the University of California, San Francisco Program for Breakthrough Biomedical Research (Y.C.). E.C. was a fellow of the Damon Runyon Cancer Research Foundation.

Author information

Author notes

    • Maofu Liao
    •  & Erhu Cao

    These authors contributed equally to this work.

Affiliations

  1. Keck Advanced Microscopy Laboratory, Department of Biochemistry and Biophysics, University of California, San Francisco, California 94158-2517, USA

    • Maofu Liao
    •  & Yifan Cheng
  2. Department of Physiology, University of California, San Francisco, California 94158-2517, USA

    • Erhu Cao
    •  & David Julius

Authors

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Contributions

All authors designed experiments. E.C. expressed and purified all protein samples used in this work and performed all functional studies. M.L. carried out all cryo-EM experiments, including data acquisition and processing. E.C. built the atomic model on the basis of cryo-EM maps. All authors analysed data and wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to David Julius or Yifan Cheng.

Extended data

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