Native-like environments afford novel mechanistic insights into membrane proteins.

Advances in cryogenic electron microscopy (cryo-EM) enabled routine near-atomic structure determination of membrane proteins, while nanodisc technology has provided a way to provide membrane proteins with a native or native-like lipid environment. After giving a brief history of membrane mimetics, we present example structures of membrane proteins in nanodiscs that revealed information not provided by structures obtained in detergent. We describe how the lipid environment surrounding the membrane protein can be custom designed during nanodisc assembly and how it can be modified after assembly to test functional hypotheses. Because nanodiscs most closely replicate the physiologic environment of membrane proteins and often afford novel mechanistic insights, we propose that nanodiscs ought to become the standard for structural studies on membrane proteins. Single-particle cryo-electron microscopy (cryo-EM) studies of membrane proteins have become routine and often yield structures at near-atomic resolution. Cryo-EM structures of membrane proteins in lipid nanodiscs often yield information not seen in structures obtained with detergent-solubilized proteins. Nanodiscs not only provide a native-like lipid environment for membrane proteins, but also make it possible to custom design and modify most aspects of the lipid bilayer. Because of the facility of generating and imaging nanodiscs by cryo-EM and because of the novel mechanistic insights into membrane protein function they can provide, nanodiscs ought to become the standard for membrane protein structure determination by single-particle cryo-EM. [ABSTRACT FROM AUTHOR]