Structural highlights
Publication Abstract from PubMed
Bestrophin calcium-activated chloride channels (CaCCs) regulate the flow of chloride and other monovalent anions across cellular membranes in response to intracellular calcium (Ca(2+)) levels. Mutations in bestrophin 1 (BEST1) cause certain eye diseases. Here we present X-ray structures of chicken BEST1-Fab complexes, at 2.85 A resolution, with permeant anions and Ca(2+). 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. Ca(2+) binds to the channel's large cytosolic region. A single ion pore, approximately 95 A 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-pi interactions. Conformational changes observed near the 'Ca(2+) clasp' hint at the mechanism of Ca(2+)-dependent gating. Disease-causing mutations are prevalent within the gating apparatus.
Structure and insights into the function of a Ca(2+)-activated Cl(-) channel.,Kane Dickson V, Pedi L, Long SB Nature. 2014 Dec 11;516(7530):213-8. doi: 10.1038/nature13913. Epub 2014 Oct 22. PMID:25337878[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Kane Dickson V, Pedi L, Long SB. Structure and insights into the function of a Ca(2+)-activated Cl(-) channel. Nature. 2014 Dec 11;516(7530):213-8. doi: 10.1038/nature13913. Epub 2014 Oct 22. PMID:25337878 doi:http://dx.doi.org/10.1038/nature13913
