Structural highlights
Publication Abstract from PubMed
Human bestrophin-1 (hBest1) is a calcium-activated chloride channel from the retinal pigment epithelium, where mutations are associated with vitelliform macular degeneration, or Best disease. We describe the structure of a bacterial homolog (KpBest) of hBest1 and functional characterizations of both channels. KpBest is a pentamer that forms a five-helix transmembrane pore, closed by three rings of conserved hydrophobic residues, and has a cytoplasmic cavern with a restricted exit. From electrophysiological analysis of structure-inspired mutations in KpBest and hBest1, we find a sensitive control of ion selectivity in the bestrophins, including reversal of anion/cation selectivity, and dramatic activation by mutations at the cytoplasmic exit. A homology model of hBest1 shows the locations of disease-causing mutations and suggests possible roles in regulation.
Structure and selectivity in bestrophin ion channels.,Yang T, Liu Q, Kloss B, Bruni R, Kalathur RC, Guo Y, Kloppmann E, Rost B, Colecraft HM, Hendrickson WA Science. 2014 Oct 17;346(6207):355-9. doi: 10.1126/science.1259723. Epub 2014 Sep, 25. PMID:25324390[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Yang T, Liu Q, Kloss B, Bruni R, Kalathur RC, Guo Y, Kloppmann E, Rost B, Colecraft HM, Hendrickson WA. Structure and selectivity in bestrophin ion channels. Science. 2014 Oct 17;346(6207):355-9. doi: 10.1126/science.1259723. Epub 2014 Sep, 25. PMID:25324390 doi:https://dx.doi.org/10.1126/science.1259723
