Details

Autor(en) / Beteiligte

• Yang, Tingting
• Liu, Qun
• Kloss, Brian
• Bruni, Renato
• Kalathur, Ravi C.
• Guo, Youzhong
• Kloppmann, Edda
• Rost, Burkhard
• Colecraft, Henry M.
• Hendrickson, Wayne A.

Titel

Structure and selectivity in bestrophin ion channels

Ist Teil von

• Science (American Association for the Advancement of Science), 2014-10, Vol.346 (6207), p.355-359

Ort / Verlag

United States: American Association for the Advancement of Science

Erscheinungsjahr

2014

Quelle

American Association for the Advancement of Science

Beschreibungen/Notizen

• 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.