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Kato, Hideaki E; Inoue, Keiichi; Abe-Yoshizumi, Rei; Kato, Yoshitaka; Ono, Hikaru; Konno, Masae; Hososhima, Shoko; Ishizuka, Toru; Hoque, Mohammad Razuanul; Kunitomo, Hirofumi; Ito, Jumpei; Yoshizawa, Susumu; Yamashita, Keitaro; Takemoto, Mizuki; Nishizawa, Tomohiro; Taniguchi, Reiya; Kogure, Kazuhiro; Maturana, Andrés D; Iino, Yuichi; Yawo, Hiromu; Ishitani, Ryuichiro; Kandori, Hideki; Nureki, Osamu
Nature (London), 05/2015, Letnik: 521, Številka: 7550Journal Article
Krokinobacter eikastus rhodopsin 2 (KR2) is the first light-driven Na(+) pump discovered, and is viewed as a potential next-generation optogenetics tool. Since the positively charged Schiff base proton, located within the ion-conducting pathway of all light-driven ion pumps, was thought to prohibit the transport of a non-proton cation, the discovery of KR2 raised the question of how it achieves Na(+) transport. Here we present crystal structures of KR2 under neutral and acidic conditions, which represent the resting and M-like intermediate states, respectively. Structural and spectroscopic analyses revealed the gating mechanism, whereby the flipping of Asp116 sequesters the Schiff base proton from the conducting pathway to facilitate Na(+) transport. Together with the structure-based engineering of the first light-driven K(+) pumps, electrophysiological assays in mammalian neurons and behavioural assays in a nematode, our studies reveal the molecular basis for light-driven non-proton cation pumps and thus provide a framework that may advance the development of next-generation optogenetics.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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in: SICRIS
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