3x3c

Publication Abstract from PubMed

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.

Structural basis for Na(+) transport mechanism by a light-driven Na(+) pump.,Kato HE, Inoue K, Abe-Yoshizumi R, Kato Y, Ono H, Konno M, Hososhima S, Ishizuka T, Hoque MR, Kunitomo H, Ito J, Yoshizawa S, Yamashita K, Takemoto M, Nishizawa T, Taniguchi R, Kogure K, Maturana AD, Iino Y, Yawo H, Ishitani R, Kandori H, Nureki O Nature. 2015 May 7;521(7550):48-53. doi: 10.1038/nature14322. Epub 2015 Apr 6. PMID:25849775^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.