Download MendeleyCrystal structure and dynamics of a lipid-induced potential desensitized-state of a pentameric ligand-gated channel.
Basak, S., Schmandt, N., Gicheru, Y., Chakrapani, S.(2017) Elife 6
- PubMed: 28262093
- DOI: https://doi.org/10.7554/eLife.23886
- Primary Citation of Related Structures:
5J0Z - PubMed Abstract:
Desensitization in pentameric ligand-gated ion channels plays an important role in regulating neuronal excitability. Here, we show that docosahexaenoic acid (DHA), a key ¦Ø-3 polyunsaturated fatty acid in synaptic membranes, enhances the agonist-induced transition to the desensitized state in the prokaryotic channel GLIC. We determined a 3.25 ? crystal structure of the GLIC-DHA complex in a potentially desensitized conformation. The DHA molecule is bound at the channel-periphery near the M4 helix and exerts a long-range allosteric effect on the pore across domain-interfaces. In this previously unobserved conformation, the extracellular-half of the pore-lining M2 is splayed open, reminiscent of the open conformation, while the intracellular-half is constricted, leading to a loss of both water and permeant ions. These findings, in combination with spin-labeling/EPR spectroscopic measurements in reconstituted-membranes, provide novel mechanistic details of desensitization in pentameric channels.
Organizational Affiliation:
Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, United States.
