4RDQ

Calcium-activated chloride channel bestrophin-1, from chicken, in complex with Fab antibody fragments, chloride and calcium

Summary for 4RDQ

• Entry DOI: 10.2210/pdb4rdq/pdb
• Descriptor: Bestrophin-1, Fab antibody fragment, light chain, Fab antibody fragment, heavy chain, ... (9 entities in total)
• Functional Keywords: transmembrane protein, membrane protein, ion channel, calcium-activated chloride channel, cacc, anion channel, membrane, transport protein
• Biological source: Gallus gallus (bantam,chickens); More
• Total number of polymer chains: 15
• Total formula weight: 479356.81

Authors

Dickson, V.K.,Pedi, L.,Long, S.B. (deposition date: 2014-09-19, release date: 2014-10-22, Last modification date: 2024-11-20)

Primary citation

Kane Dickson, V.,Pedi, L.,Long, S.B.
Structure and insights into the function of a Ca(2+)-activated Cl(-) channel.
Nature, 516:213-218, 2014

PubMed Abstract: 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 Å 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 Å 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 'Ca(2+) clasp' hint at the mechanism of Ca(2+)-dependent gating. Disease-causing mutations are prevalent within the gating apparatus.

PubMed: 25337878
DOI: 10.1038/nature13913

Experimental method

X-RAY DIFFRACTION (2.85 Å)