Nanodiscs remain indispensable for Cryo-EM studies of membrane proteins

Nanodiscs, small discoidal membrane patches stabilized by membrane-scaffold proteins (MSPs), are popular tools to stabilize integral membrane proteins (IMPs) for structural studies by cryogenic electron microscopy (cryo-EM). While nanodiscs provide a near-native membrane environment for the incorporated IMPs, they do not reproduce all characteristics of a native membrane. Also, IMPs must first be purified in detergent before they can be reconstituted into MSP-based nanodiscs, a problem that has been overcome by newer approaches, such as copolymer-based native nanodiscs and cell-derived vesicles. In this review, we argue that despite these advances, MSP-based nanodiscs remain a unique tool for the structural interrogation of IMPs.