Structure and insights into the function of a Ca2+-activated Cl- channel Journal Article
| Authors: | Dickson, V. K.; Pedi, L.; Long, S. B. |
| Article Title: | Structure and insights into the function of a Ca2+-activated Cl- channel |
| Abstract: | Bestrophin calcium-activated chloride channels (CaCCs) regulate the flow of chloride and other monovalent anions across cellular membranes in response to intracellular calcium (Ca2+) levels. Mutations in bestrophin 1 (BEST1) cause certain eye diseases. Here we present X-ray structures of chicken BEST1-Fab complexes, at 2.85A° resolution, with permeant anions and Ca2+. Representing, to our knowledge, the first structure of a CaCC, the eukaryotic BEST1 channel, which recapitulates CaCC function in liposomes, is formed from a pentameric assembly of subunits. Ca2+ binds to the channel's large cytosolic region. A single ion pore, approximately 95A° in length, is located along the central axis and contains at least 15 binding sites for anions. A hydrophobic neck within the pore probably forms the gate. Phenylalanine residues within it may coordinate permeating anions via anion-π interactions. Conformational changes observed near the 'Ca2+ clasp' hint at the mechanism of Ca2+-dependent gating. Disease-causing mutations are prevalent within the gating apparatus. |
| Keywords: | eukaryota |
| Journal Title: | Nature |
| Volume: | 516 |
| Issue: | 7530 |
| ISSN: | 0028-0836 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2014-12-11 |
| Start Page: | 213 |
| End Page: | 218 |
| Language: | English |
| DOI: | 10.1038/nature13913 |
| PROVIDER: | scopus |
| PUBMED: | 25337878 |
| PMCID: | PMC4454446 |
| DOI/URL: | |
| Notes: | Export Date: 2 March 2015 -- Source: Scopus |
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