Lipid nanodisc scaffold and size alter the structure of a pentameric ligand-gated ion channel

Vikram Dalal, Mark J. Arcario, John T. Petroff, Brandon K. Tan, Noah M. Dietzen, Michael J. Rau, James A. J. Fitzpatrick, Grace Brannigan and Wayland W. L. Cheng ()
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Vikram Dalal: Washington University School of Medicine
Mark J. Arcario: Washington University School of Medicine
John T. Petroff: Washington University School of Medicine
Brandon K. Tan: Washington University School of Medicine
Noah M. Dietzen: Washington University School of Medicine
Michael J. Rau: Washington University School of Medicine
James A. J. Fitzpatrick: Washington University School of Medicine
Grace Brannigan: Rutgers University
Wayland W. L. Cheng: Washington University School of Medicine

Nature Communications, 2024, vol. 15, issue 1, 1-10

Abstract: Abstract Lipid nanodiscs have become a standard tool for studying membrane proteins, including using single particle cryo-electron microscopy (cryo-EM). We find that reconstituting the pentameric ligand-gated ion channel (pLGIC), Erwinia ligand-gated ion channel (ELIC), in different nanodiscs produces distinct structures by cryo-EM. The effect of the nanodisc on ELIC structure extends to the extracellular domain and agonist binding site. Additionally, molecular dynamic simulations indicate that nanodiscs of different size impact ELIC structure and that the nanodisc scaffold directly interacts with ELIC. These findings suggest that the nanodisc plays a crucial role in determining the structure of pLGICs, and that reconstitution of ion channels in larger nanodiscs may better approximate a lipid membrane environment.

Date: 2024
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DOI: 10.1038/s41467-023-44366-w

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