1. Structural Biology and Molecular Biophysics
Download icon

Irreversible temperature gating in trpv1 sheds light on channel activation

Short Report
  • Cited 15
  • Views 2,272
  • Annotations
Cite this article as: eLife 2018;7:e36372 doi: 10.7554/eLife.36372

Abstract

Temperature activated TRP channels or thermoTRPs are among the only proteins that can directly convert temperature changes into changes in channel open probability. In spite of a wealth of functional and structural information, the mechanism of temperature activation remains unknown. We have carefully characterized the repeated activation of TRPV1 by thermal stimuli and discovered a previously unknown inactivation process, which is irreversible. We propose that this form of gating in TRPV1 channels is a consequence of the heat absorption process that leads to channel opening.

Article and author information

Author details

  1. Ana Sánchez-Moreno

    Departamento de Fisiología, Universidad Nacional Autónoma de México, México City, Mexico
    Competing interests
    No competing interests declared.
  2. Eduardo Guevara-Hernández

    Departamento de Fisiología, Universidad Nacional Autónoma de México, México City, Mexico
    Competing interests
    No competing interests declared.
  3. Ricardo Contreras-Cervera

    Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México City, Mexico
    Competing interests
    No competing interests declared.
  4. Gisela Rangel-Yescas

    Departamento de Fisiología, Universidad Nacional Autónoma de México, México City, Mexico
    Competing interests
    No competing interests declared.
  5. Ernesto Ladrón-de-Guevara

    Departamento de Fisiología, Universidad Nacional Autónoma de México, México City, Mexico
    Competing interests
    No competing interests declared.
  6. Tamara Rosenbaum

    Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México City, Mexico
    Competing interests
    No competing interests declared.
  7. Leon D Islas

    Departamento de Fisiología, Universidad Nacional Autónoma de México, México City, Mexico
    For correspondence
    leon.islas@gmail.com
    Competing interests
    Leon D Islas, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7461-5214

Funding

Consejo Nacional de Ciencia y Tecnología (CB-2015-252644)

  • Leon D Islas

DGAPA-PAPIIT-UNAM (IN209515)

  • Leon D Islas

DGAPA-PAPIITT-UNAM (IN200717)

  • Tamara Rosenbaum

Consejo Nacional de Ciencia y Tecnología (CB-2014-01-238399)

  • Tamara Rosenbaum

Consejo Nacional de Ciencia y Tecnología (Fronteras de la Ciencia 77)

  • Tamara Rosenbaum
  • Leon D Islas

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Baron Chanda, University of Wisconsin-Madison, United States

Publication history

  1. Received: March 3, 2018
  2. Accepted: May 26, 2018
  3. Accepted Manuscript published: June 5, 2018 (version 1)
  4. Version of Record published: June 13, 2018 (version 2)

Copyright

© 2018, Sánchez-Moreno et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 2,272
    Page views
  • 467
    Downloads
  • 15
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, Scopus, PubMed Central.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

  1. Further reading

Further reading

    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics
    Palur V Raghuvamsi et al.
    Research Article Updated

    The spike (S) protein is the main handle for SARS-CoV-2 to enter host cells via surface angiotensin-converting enzyme 2 (ACE2) receptors. How ACE2 binding activates proteolysis of S protein is unknown. Here, using amide hydrogen–deuterium exchange mass spectrometry and molecular dynamics simulations, we have mapped the S:ACE2 interaction interface and uncovered long-range allosteric propagation of ACE2 binding to sites necessary for host-mediated proteolysis of S protein, critical for viral host entry. Unexpectedly, ACE2 binding enhances dynamics at a distal S1/S2 cleavage site and flanking protease docking site ~27 Å away while dampening dynamics of the stalk hinge (central helix and heptad repeat [HR]) regions ~130 Å away. This highlights that the stalk and proteolysis sites of the S protein are dynamic hotspots in the prefusion state. Our findings provide a dynamics map of the S:ACE2 interface in solution and also offer mechanistic insights into how ACE2 binding is allosterically coupled to distal proteolytic processing sites and viral–host membrane fusion. Thus, protease docking sites flanking the S1/S2 cleavage site represent alternate allosteric hotspot targets for potential therapeutic development.

    1. Structural Biology and Molecular Biophysics
    Fangyu Liu et al.
    Research Article Updated

    The ATP-binding cassette (ABC) transporter family contains thousands of members with diverse functions. Movement of the substrate, powered by ATP hydrolysis, can be outward (export) or inward (import). ABCA4 is a eukaryotic importer transporting retinal to the cytosol to enter the visual cycle. It also removes toxic retinoids from the disc lumen. Mutations in ABCA4 cause impaired vision or blindness. Despite decades of clinical, biochemical, and animal model studies, the molecular mechanism of ABCA4 is unknown. Here, we report the structures of human ABCA4 in two conformations. In the absence of ATP, ABCA4 adopts an outward-facing conformation, poised to recruit substrate. The presence of ATP induces large conformational changes that could lead to substrate release. These structures provide a molecular basis to understand many disease-causing mutations and a rational guide for new experiments to uncover how ABCA4 recruits, flips, and releases retinoids.