Structural basis for Na + transport mechanism by a light-driven Na + pump

Hideaki E. Kato, Keiichi Inoue, Rei Abe-Yoshizumi, Yoshitaka Kato, Hikaru Ono, Masae Konno, Shoko Hososhima, Toru Ishizuka, Mohammad Razuanul Hoque, Hirofumi Kunitomo, Jumpei Ito, Susumu Yoshizawa, Keitaro Yamashita, Mizuki Takemoto, Tomohiro Nishizawa, Reiya Taniguchi, Kazuhiro Kogure, Andrés D. Maturana, Yuichi Iino, Hiromu YawoRyuichiro Ishitani, Hideki Kandori, Osamu Nureki

    Research output: Contribution to journalArticlepeer-review

    109 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish
    Pages (from-to)48-53
    Number of pages6
    JournalNature
    Volume521
    Issue number7550
    DOIs
    Publication statusPublished - 2015 May 7

    ASJC Scopus subject areas

    • General

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