Structural determinants of ion permeation in CRAC channels

• DOI: 10.1073/pnas.0909574106
• Publication Date: 2009-12-12T02:31:03Z
• Authors: Beth A. McNally; Megumi Yamashita; Anita Engh; Murali Prakriya
• Keywords: Orai1; KcsA potassium channel

CRAC channels generate Ca(2+) signals critical for the activation of immune cells and exhibit an intriguing pore profile distinguished by extremely high selectivity, low Cs(+) permeability, small unitary conductance. To identify ion conduction pathway gain insight into structural bases these permeation characteristics, we introduced cysteine residues in channel subunit, Orai1, probed their accessibility to various thiol-reactive reagents. Our results indicate that architecture is characterized a flexible outer vestibule formed TM1-TM2 loop, which leads narrow flanked helical TM1 segment. Residues TM3, specifically, E190, residue considered important are not close pore. Moreover, does significantly contribute implying selectivity conferred mainly E106. The sufficiently along much its length permit stable coordination Cd(2+) several residues, likely explains slow flux ions within restrained geometry These provide framework understand unique properties channels.