Zeev-Ben-Mordehai, T. et al. Nat. Commun. 5, 3912 (2014).

Membrane proteins are tricky for structural biologists to handle because they typically require laborious and expensive solubilization, purification and reconstitution approaches that usually result in very low protein yields and may compromise protein function. Zeev-Ben-Mordehai et al. used a simple yet elegant approach to display a membrane protein on cell-derived membrane vesicles in the topologically correct orientation. Overexpressing the target resulted in the accumulation of target-enriched, membrane-derived extracellular vesicles. The vesicles could then be isolated by differential centrifugation and were immediately ready for three-dimensional structural analysis by cryo-electron microscopy (cryo-EM). The approach enabled the researchers to determine a cryo-EM three-dimensional structure for a Caenorhabditis elegans cell-cell fusion protein, epithelial fusion failure 1 (EFF-1), and led them to propose a model for EFF-1–mediated fusion.