The structure of a calcium-independent BEST1 mutant (I76A, F80A, F84A). One of the five subunits is removed to show the pore, and the magenta spheres are chloride atoms just above the pore entrance.
The group of Stephen Long at the Memorial Sloan Kettering Cancer Center used X-ray crystallography at GM/CA@APS and at the NSLS to study the function of the bestrophin (BEST1) ion channel. BEST1 is a calcium-activated chloride channel found in the plasma membrane of a variety of cell types. Mutations in BEST1 can cause macular degeneration. Calcium binding to the cytoplasmic region of the BEST1 channel causes channel opening. This work identifies a calcium-dependent channel gate consisting of three conserved hydrophobic amino acids. The researchers determined a high-resolution structure of a gate mutant using data from 23ID-D to show how widening the pore in the gate region leads to calcium-independent activity.
Vaisey G, Miller AN, Long SB, "Distinct regions that control ion selectivity and calcium-dependent activation in the bestrophin ion channel," Proc. Natl. Acad. Sci. USA 113 (47), E7399-E7408 (2016). DOI: 10.1073/pnas.1614688113