Structure of the human ClC-1 chloride channel

Research output: Contribution to journalJournal articleResearchpeer-review

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Structure of the human ClC-1 chloride channel. / Wang, Kaituo; Preisler, Sarah Spruce; Zhang, Liying; Cui, Yanxiang; Missel, Julie Winkel; Grønberg, Christina; Gotfryd, Kamil; Lindahl, Erik; Andersson, Magnus; Calloe, Kirstine; Egea, Pascal F; Klaerke, Dan Arne; Pusch, Michael; Pedersen, Per Amstrup; Zhou, Z. Hong; Gourdon, Pontus.

In: PLOS Biology, Vol. 17, No. 4, e3000218, 2019, p. 1-20.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Wang, K, Preisler, SS, Zhang, L, Cui, Y, Missel, JW, Grønberg, C, Gotfryd, K, Lindahl, E, Andersson, M, Calloe, K, Egea, PF, Klaerke, DA, Pusch, M, Pedersen, PA, Zhou, ZH & Gourdon, P 2019, 'Structure of the human ClC-1 chloride channel', PLOS Biology, vol. 17, no. 4, e3000218, pp. 1-20. https://doi.org/10.1371/journal.pbio.3000218

APA

Wang, K., Preisler, S. S., Zhang, L., Cui, Y., Missel, J. W., Grønberg, C., Gotfryd, K., Lindahl, E., Andersson, M., Calloe, K., Egea, P. F., Klaerke, D. A., Pusch, M., Pedersen, P. A., Zhou, Z. H., & Gourdon, P. (2019). Structure of the human ClC-1 chloride channel. PLOS Biology, 17(4), 1-20. [e3000218]. https://doi.org/10.1371/journal.pbio.3000218

Vancouver

Wang K, Preisler SS, Zhang L, Cui Y, Missel JW, Grønberg C et al. Structure of the human ClC-1 chloride channel. PLOS Biology. 2019;17(4):1-20. e3000218. https://doi.org/10.1371/journal.pbio.3000218

Author

Wang, Kaituo ; Preisler, Sarah Spruce ; Zhang, Liying ; Cui, Yanxiang ; Missel, Julie Winkel ; Grønberg, Christina ; Gotfryd, Kamil ; Lindahl, Erik ; Andersson, Magnus ; Calloe, Kirstine ; Egea, Pascal F ; Klaerke, Dan Arne ; Pusch, Michael ; Pedersen, Per Amstrup ; Zhou, Z. Hong ; Gourdon, Pontus. / Structure of the human ClC-1 chloride channel. In: PLOS Biology. 2019 ; Vol. 17, No. 4. pp. 1-20.

Bibtex

@article{97d3bf2124454b2f84ae55bde4c715bc,
title = "Structure of the human ClC-1 chloride channel",
abstract = "ClC-1 protein channels facilitate rapid passage of chloride ions across cellular membranes, thereby orchestrating skeletal muscle excitability. Malfunction of ClC-1 is associated with myotonia congenita, a disease impairing muscle relaxation. Here, we present the cryo-electron microscopy (cryo-EM) structure of human ClC-1, uncovering an architecture reminiscent of that of bovine ClC-K and CLC transporters. The chloride conducting pathway exhibits distinct features, including a central glutamate residue ({"}fast gate{"}) known to confer voltage-dependence (a mechanistic feature not present in ClC-K), linked to a somewhat rearranged central tyrosine and a narrower aperture of the pore toward the extracellular vestibule. These characteristics agree with the lower chloride flux of ClC-1 compared with ClC-K and enable us to propose a model for chloride passage in voltage-dependent CLC channels. Comparison of structures derived from protein studied in different experimental conditions supports the notion that pH and adenine nucleotides regulate ClC-1 through interactions between the so-called cystathionine-β-synthase (CBS) domains and the intracellular vestibule ({"}slow gating{"}). The structure also provides a framework for analysis of mutations causing myotonia congenita and reveals a striking correlation between mutated residues and the phenotypic effect on voltage gating, opening avenues for rational design of therapies against ClC-1-related diseases.",
author = "Kaituo Wang and Preisler, {Sarah Spruce} and Liying Zhang and Yanxiang Cui and Missel, {Julie Winkel} and Christina Gr{\o}nberg and Kamil Gotfryd and Erik Lindahl and Magnus Andersson and Kirstine Calloe and Egea, {Pascal F} and Klaerke, {Dan Arne} and Michael Pusch and Pedersen, {Per Amstrup} and Zhou, {Z. Hong} and Pontus Gourdon",
year = "2019",
doi = "10.1371/journal.pbio.3000218",
language = "English",
volume = "17",
pages = "1--20",
journal = "P L o S Biology",
issn = "1544-9173",
publisher = "Public Library of Science",
number = "4",

}

RIS

TY - JOUR

T1 - Structure of the human ClC-1 chloride channel

AU - Wang, Kaituo

AU - Preisler, Sarah Spruce

AU - Zhang, Liying

AU - Cui, Yanxiang

AU - Missel, Julie Winkel

AU - Grønberg, Christina

AU - Gotfryd, Kamil

AU - Lindahl, Erik

AU - Andersson, Magnus

AU - Calloe, Kirstine

AU - Egea, Pascal F

AU - Klaerke, Dan Arne

AU - Pusch, Michael

AU - Pedersen, Per Amstrup

AU - Zhou, Z. Hong

AU - Gourdon, Pontus

PY - 2019

Y1 - 2019

N2 - ClC-1 protein channels facilitate rapid passage of chloride ions across cellular membranes, thereby orchestrating skeletal muscle excitability. Malfunction of ClC-1 is associated with myotonia congenita, a disease impairing muscle relaxation. Here, we present the cryo-electron microscopy (cryo-EM) structure of human ClC-1, uncovering an architecture reminiscent of that of bovine ClC-K and CLC transporters. The chloride conducting pathway exhibits distinct features, including a central glutamate residue ("fast gate") known to confer voltage-dependence (a mechanistic feature not present in ClC-K), linked to a somewhat rearranged central tyrosine and a narrower aperture of the pore toward the extracellular vestibule. These characteristics agree with the lower chloride flux of ClC-1 compared with ClC-K and enable us to propose a model for chloride passage in voltage-dependent CLC channels. Comparison of structures derived from protein studied in different experimental conditions supports the notion that pH and adenine nucleotides regulate ClC-1 through interactions between the so-called cystathionine-β-synthase (CBS) domains and the intracellular vestibule ("slow gating"). The structure also provides a framework for analysis of mutations causing myotonia congenita and reveals a striking correlation between mutated residues and the phenotypic effect on voltage gating, opening avenues for rational design of therapies against ClC-1-related diseases.

AB - ClC-1 protein channels facilitate rapid passage of chloride ions across cellular membranes, thereby orchestrating skeletal muscle excitability. Malfunction of ClC-1 is associated with myotonia congenita, a disease impairing muscle relaxation. Here, we present the cryo-electron microscopy (cryo-EM) structure of human ClC-1, uncovering an architecture reminiscent of that of bovine ClC-K and CLC transporters. The chloride conducting pathway exhibits distinct features, including a central glutamate residue ("fast gate") known to confer voltage-dependence (a mechanistic feature not present in ClC-K), linked to a somewhat rearranged central tyrosine and a narrower aperture of the pore toward the extracellular vestibule. These characteristics agree with the lower chloride flux of ClC-1 compared with ClC-K and enable us to propose a model for chloride passage in voltage-dependent CLC channels. Comparison of structures derived from protein studied in different experimental conditions supports the notion that pH and adenine nucleotides regulate ClC-1 through interactions between the so-called cystathionine-β-synthase (CBS) domains and the intracellular vestibule ("slow gating"). The structure also provides a framework for analysis of mutations causing myotonia congenita and reveals a striking correlation between mutated residues and the phenotypic effect on voltage gating, opening avenues for rational design of therapies against ClC-1-related diseases.

U2 - 10.1371/journal.pbio.3000218

DO - 10.1371/journal.pbio.3000218

M3 - Journal article

C2 - 31022181

VL - 17

SP - 1

EP - 20

JO - P L o S Biology

JF - P L o S Biology

SN - 1544-9173

IS - 4

M1 - e3000218

ER -

ID: 217156477