umu.sePublications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Structure of the human ClC-1 chloride channel
Show others and affiliations
2019 (English)In: PLoS biology, ISSN 1544-9173, E-ISSN 1545-7885, Vol. 17, no 4, article id e3000218Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Public Library Science , 2019. Vol. 17, no 4, article id e3000218
National Category
Biochemistry and Molecular Biology
Identifiers
URN: urn:nbn:se:umu:diva-159072DOI: 10.1371/journal.pbio.3000218ISI: 000466600400031PubMedID: 31022181OAI: oai:DiVA.org:umu-159072DiVA, id: diva2:1316902
Available from: 2019-05-21 Created: 2019-05-21 Last updated: 2019-05-21Bibliographically approved

Open Access in DiVA

fulltext(3763 kB)54 downloads
File information
File name FULLTEXT01.pdfFile size 3763 kBChecksum SHA-512
f0d47f9433b2e20c75ef259d9b0877046944e00444ce3f50fc112e2f5da5ba23f7a846e3c51a71fd6d9732fd3973e75a6a44034d943da59d1fdd07af0be67f71
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Authority records BETA

Andersson, Magnus

Search in DiVA

By author/editor
Andersson, MagnusEgea, Pascal F.
By organisation
Department of Chemistry
In the same journal
PLoS biology
Biochemistry and Molecular Biology

Search outside of DiVA

GoogleGoogle Scholar
Total: 54 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 121 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf