Seiya Tajima, Yoon Seok Kim, Masahiro Fukuda, YoungJu Jo, Peter Y Wang, Joseph M Paggi, Masatoshi Inoue, Eamon F X Byrne, Koichiro E Kishi, Seiwa Nakamura, Charu Ramakrishnan, Shunki Takaramoto, Takashi Nagata, Masae Konno, Masahiro Sugiura, Kota Katayama, Toshiki E Matsui, Keitaro Yamashita, Suhyang Kim, Hisako Ikeda, Jaeah Kim, Hideki Kandori, Ron O Dror, Keiichi Inoue, Karl Deisseroth, Hideaki E Kato
KCR channelrhodopsins (K+ -selective light-gated ion channels) have received attention as potential inhibitory optogenetic tools but more broadly pose a fundamental mystery regarding how their K+ selectivity is achieved. Here, we present 2.5-2.7 Å cryo-electron microscopy structures of HcKCR1 and HcKCR2 and of a structure-guided mutant with enhanced K+ selectivity. Structural, electrophysiological, computational, spectroscopic, and biochemical analyses reveal a distinctive mechanism for K+ selectivity; rather than forming the symmetrical filter of canonical K+ channels achieving both selectivity and dehydration, instead, three extracellular-vestibule residues within each monomer form a flexible asymmetric selectivity gate, while a distinct dehydration pathway extends intracellularly...
September 28, 2023: Cell