Journal
NATURE
Volume 521, Issue 7550, Pages 48-U347Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nature14322
Keywords
-
Categories
Funding
- Platform for Drug Discovery, Informatics and Structural Life Science, of the Ministry of Education, Culture, Sports, Science and Technology (MEXT)
- JSPS KAKENHI [11J06643, 24115508, 24655009, 25104009, 24681003, 24227004, 25291011]
- FIRST program, PRESTO, CREST, JST
- Grants-in-Aid for Scientific Research [24681003, 26708001, 24115508, 26430007, 25115707, 15H02391, 11J06643, 22247024, 25250001, 26291069, 25670103, 25104009, 15J06631, 26115706, 26620005, 25115701, 15J08129, 15H02800, 14J40214, 15K15025, 24655009, 25115010, 25620011, 15H01413] Funding Source: KAKEN
Ask authors/readers for more resources
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 K1 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available