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Structure of a Eukaryotic CLC Transporter Defines an Intermediate State in the Transport Cycle
Abstract
Controlling Chloride Channels: The CLC proteins are a large family of channels and transporters that transfer chloride ions across cell membranes. While structures of two prokaryotic CLCs have been determined, these do not include the cytoplasmic regulatory domains found in eukaryotic transporters, and the structures do not reveal the mechanism of Cl − /H + –coupled transport. L. Feng et al. (p. 635 , published online 30 September; see the Perspective by Mindell ) describe the structure of a eukaryotic CLC protein and found that the regulatory domains interacted closely with the transmembrane domain so that conformational changes are transmitted to the ion pathway. A gating glutamate in the eukaryote transporter is in a different conformation to prokaryotic structures, explaining the 2:1 stoichiometry of Cl − /H + exchange in eukaryotes.
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A number of Cl− transporting CLCs have been structurally characterized, providing a deep mechanistic basis for understanding the fluoride riboswitch-associated CLCs.
“A number of Cl− transporting CLCs have been structurally characterized, providing a deep mechanistic basis for understanding the fluoride riboswitch-associated CLCs (42–46).”
From Membrane exporters of fluoride ion (2021) · cites this paper as [44]
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The Cl-/H+ antiporter ClC-7 is the primary chloride permeation pathway in lysosomes
Graves, A. R., Curran, P. K., Smith, C. L., & Mindell, J. A. (2008) · Nature · doi:10.1038/nature06907 · Cited by 399
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Lysosomal acidification mechanisms
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Mechanism of Fatty-Acid-Dependent UCP1 Uncoupling in Brown Fat Mitochondria
Fedorenko, A., Lishko, P. V., & Kirichok, Y. (2012) · Cell · doi:10.1016/j.cell.2012.09.010 · Cited by 968
Membrane exporters of fluoride ion
McIlwain, B. C., Ruprecht, M. T., & Stockbridge, R. B. (2021) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-071520-112507 · Cited by 69
Protein p K a Prediction by Tree-Based Machine Learning
Chen, A. Y., Lee, J., Damjanovic, A., & Brooks, B. R. (2022) · Journal of Chemical Theory and Computation · doi:10.1021/acs.jctc.1c01257 · Cited by 37
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Structural insights into pink-eyed dilution protein (Oca2)
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A large‐scale evolutionary and structural analysis of CLC channels and transporters
Mishra, A., Díaz Vázquez, G., & Robertson, J. L. (2025) · Protein Science · doi:10.1002/pro.70389 · Cited by 3
“…this switch occurred, denoted the transition region, was defined as a low-resolution region of the tree containing both channel and transporter homologs, including transporter cmCLC (Feng et al., 2010) and channel ngCLC (Fortea Verdejo, 2021), located between two nodes with 96% support (Figure 2d).”
Metadata
- Authors
- Feng, L., Campbell, E. B., Hsiung, Y., & MacKinnon, R.
- Affiliations
- Laboratory of Molecular Neurobiology and Biophysics, Rockefeller University, Howard Hughes Medical Institute, 1230 York Avenue, New York, NY 10065, USA.
- Venue
- Science
- Published
- 2010-10-29
- Volume
- 330
- Issue
- 6004
- Pages
- 635-641
- ISSN
- 0036-8075
- 1095-9203
- PMC
- PMC3079386
- Cited by
- 270
- References
- 1
- Language
- en
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