5j0z

Publication Abstract from PubMed

Desensitization in pentameric ligand-gated ion channels plays an important role in regulating neuronal excitability. Here, we show that docosahexaenoic acid (DHA), a key omega-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 A 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.

Crystal structure and dynamics of a lipid-induced potential desensitized-state of a pentameric ligand-gated channel.,Basak S, Schmandt N, Gicheru Y, Chakrapani S Elife. 2017 Mar 6;6. pii: 23886. doi: 10.7554/eLife.23886. PMID:28262093^[2]

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