The crystal structure of bromide-bound GtACR1 reveals a pre-activated state in the transmembrane anion tunnel
- University of Texas Health Science Center at Houston, McGovern Medical School, United States
- Swiss Light Source, Paul Scherrer Institute, Switzerland
- Boston University, United States
Abstract
The crystal structure of the light-gated anion channel GtACR1 reported in our previous Research Article (Li et al., 2019) revealed a continuous tunnel traversing the protein from extracellular to intracellular pores. We proposed the tunnel as the conductance channel closed by three constrictions: C1 in the extracellular half, mid-membrane C2 containing the photoactive site, and C3 on the cytoplasmic side. Reported here, the crystal structure of bromide-bound GtACR1 reveals structural changes that relax the C1 and C3 constrictions, including a novel salt-bridge switch mechanism involving C1 and the photoactive site. These findings indicate that substrate binding induces a transition from an inactivated state to a pre-activated state in the dark that facilitates channel opening by reducing free energy in the tunnel constrictions. The results provide direct evidence that the tunnel is the closed form of the channel of GtACR1 and shed light on the light-gated channel activation mechanism.
Data availability
Diffraction data have been deposited in PDB under the accession code 7L1E.
Article and author information
Author details
Elena G Govorunova
Funding
National Institute of General Medical Sciences (R01GM027750)
- John L Spudich
National Institute of General Medical Sciences (R35GM140838)
- John L Spudich
Robert A. Welch Foundation (Endowed Chair AU-0009)
- John L Spudich
American Heart Association (18TPA34230046)
- Lei Zheng
National Science Foundation (CBET-1264434)
- Kenneth J Rothschild
European Union's Horizon 2020 (Marie-Skłodowska-Curie grant agreement No. 701647)
- Chia-Ying Huang
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Sriram Subramaniam, University of British Columbia, Canada
Version history
- Received: December 31, 2020
- Accepted: May 16, 2021
- Accepted Manuscript published: May 17, 2021 (version 1)
- Version of Record published: June 2, 2021 (version 2)
Copyright
© 2021, Li 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.
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The crystal structure of bromide-bound GtACR1 reveals a pre-activated state in the transmembrane anion tunnel
eLife 10:e65903.
https://doi.org/10.7554/eLife.65903
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