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Probing solution structure of the pentameric ligand-gated ion channel GLIC by small-angle neutron scattering

2021; National Academy of Sciences; Volume: 118; Issue: 37 Linguagem: Inglês

10.1073/pnas.2108006118

1091-6490

Marie Lycksell, Urška Rovšnik, Cathrine Bergh, Nicolai Tidemand Johansen, Anne Martel, Lionel Porcar, Lise Arleth, Rebecca J. Howard, Erik Lindahl,

Mass Spectrometry Techniques and Applications

Significance Ligand-gated ion channels are membrane proteins that cycle rapidly between open and closed forms, a process called gating. The structural basis of gating is foundational to receptor biophysics, cellular physiology, and drug design; however, it remains unclear how experimental X-ray structures correspond to solution behavior. Here, we test the solution structure of a model ion channel, GLIC, based on small-angle neutron scattering and molecular simulations under conditions that favor closed or open states. We find that closed-state conditions correspond well to closed X-ray structures, while open-state conditions implicate intermediate or mixed open/closed structures. These results elucidate the states sampled during ion channel gating, and the utility of neutron scattering combined with simulations to distinguish subtle shifts in membrane protein structure.