TRAP builds a better translocon

For over a decade, mechanistic studies of protein translocation into the mammalian ER have relied on proteoliposomes with translocons reconstituted from purified components, a system that efficiently translocates simple model proteins like prolactin, but often fails to match in vivo translocation efficiency for other substrates. On page 529, Fons et al. explain why by showing that the TRAP complex, previously considered dispensable for translocation, is actually a substrate-specific functional component of the mammalian translocon. The work suggests that accessory complexes like TRAP could help to drive both normal and pathological cell physiology.

In the standard reconstituted system, prion protein (PrP) either fails to translocate or becomes stuck as a transmembrane protein, problems that are also observed in some neurodegenerative prion diseases. The authors exploited this defect to purify a factor that stimulates complete translocation of...