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

• Autores: Hideaki E. Kato, Keiichi Inoue, Rei Abe Yoshizumi, Yoshitaka Kato, Hikaru Ono, Masae Konno
• Localización: Nature: International weekly journal of science, ISSN 0028-0836, Vol. 521, Nº 7550, 2015, págs. 48-53
• Idioma: inglés
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• Resumen

  • 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.