@article{TEXTUAL,
      recid = {9888},
      author = {Basak, Sandip and Schmandt, Nicolaus and Gicheru, Yvonne  and Chakrapani, Sudha},
      title = {Crystal structure and dynamics of a lipid-induced  potential desensitized-state of a pentameric ligand-gated  channel},
      journal = {eLife},
      address = {2017-03-06},
      number = {TEXTUAL},
      abstract = {Desensitization in pentameric ligandgated ion channels  plays an important role in regulating neuronal  excitability. Here, we show that docosahexaenoic acid  (DHA), a key ω−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 Å 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 porelining 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.},
      url = {http://knowledge.uchicago.edu/record/9888},
}