Eyckerman, S. et al. Nat. Commun. 7, 11416 (2016).

Affinity purification–mass spectrometry, wherein a bait protein is tagged with a purification handle, is widely used to capture and identify protein interactions. The method, however, is highly dependent on lysis and purification conditions, which can have a substantial impact on the results. As a way to avoid the potential pitfalls, Eyckerman et al. developed a method called Virotrap, which avoids cell lysis and helps preserve protein interactions during affinity purification. In this approach, a bait protein is fused to HIV-1 Gag, which results in its accumulation at a mammalian cell membrane and subsequent budding off of virus-like particles. The virus-like particles containing bait–prey complexes can be readily sorted and the prey proteins can be identified using western blotting or mass spectrometry. The authors show that Virotrap confirms known protein interactions and reveals novel interactions as well.