Biochemistry, Biophysics, and Structural Biology Commons^™

Peregrination Of The Selectivity Filter Delineates The Pore Of The Human Voltage-Gated Proton Channel Hhv1, Deri Morgan, Boris Musset, Kethika Kulleperuma, Susan M. E. Smith, Sindhu Rajan, Vladimir V. Cherny, Régis Pomès, Thomas E. Decoursey

Faculty and Research Publications

Extraordinary selectivity is crucial to all proton-conducting molecules, including the human voltage-gated proton channel (hH_v1), because the proton concentration is >10⁶ times lower than that of other cations. Here we use "selectivity filter scanning" to elucidate the molecular requirements for proton-specific conduction in hH_v1. Asp¹¹², in the middle of the S1 transmembrane helix, is an essential part of the selectivity filter in wild-type (WT) channels. After neutralizing Asp¹¹² by mutating it to Ala (D112A), we introduced Asp at each position along S1 from 108 to 118, searching for "second site suppressor" activity. …