Northwestern Events Calendar

Dec
2
2021

Research Seminar (Introduction by Talia Lerner) - “Inner workings of channelrhodopsins and brains”

When: Thursday, December 2, 2021
3:00 PM - 4:00 PM Central

Where: Online

Audience: Faculty/Staff - Student - Post Docs/Docs - Graduate Students

Contact: NUIN   (312) 503-4300

Group: NUIN Calendar

Category: Academic, Lectures & Meetings

Description:

“Inner workings of channelrhodopsins and brains” 

The remarkable family of light-activated ion channels, or channelrhodopsins, span three main groups (the cation channels, the anion channels, and the pump-like channels).  We have previously described the first high-resolution structures of the first two groups (cation and anion channels), and used these insights to redesign the channels for new kinds of function in optogenetics, but the third family of channelrhodopsins had remained mysterious. For example, ChRmine (the paradigmatic member of this pump-like channelrhodopsin family, for which we reported initial discovery in 2019) exhibits puzzling properties (unusually-large photocurrents, exceptional red-shift in action spectrum, and extreme light-sensitivity) that opened up new opportunities in optogenetics, including the initial definition and control of specific mammalian perceptions at single cell resolution. In this talk I will present our new cryo-electron microscopy structure of ChRmine at 2.0 Å resolution. The structure reveals striking architectural features never seen before in channelrhodopsins including trimeric assembly, a short transmembrane-helix 3 unwound in the middle of the membrane, a prominently-twisting extracellular-loop 1, remarkably-large intracellular cavities and extracellular vestibule, and an unprecedented hydrophilic pore that extends through the center of the trimer, separate from the three individual monomer pores. These structurally distinct features that may enable ChRmine (representing the third of the three major branches of the channelrhodopsin family) to function as an especially potent ion channel; we therefore applied the high-resolution structure to design and create two new proteins (rsChRmine and hsChRmine, for red-shifted and high-speed optogenetic performance, respectively). Insights into complex behavior that have emerged from Ångstrom-level understanding of these proteins include deeper understanding of the fundamental survival drives of animals at single-cell resolution, and of the highest-level integrative functions of the brain, with both basic-science and clinical implications.

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