Formation of Transmembrane Helices In Vivo—Is Hydrophobicity All that Matters?

While many generalizations about membrane protein assembly and structure have been formulated over the years, most recently based on the rapidly growing database of high-resolution three-dimensional membrane protein structures (White, 2004), a quantitative understanding of the underlying principles is mostly lacking, at least for in vivo conditions. To address this issue, we have developed an experimental system based on in vitro translation of model membrane proteins in the presence of dog pancreas rough microsomes that makes it possible to measure the efficiency with which different natural or designed polypeptide segments insert into the ER membrane under conditions approximating the in vivo situation (Sääf et al., 1998; Hessa et al., 2005a,b; Meindl-Beinker et al., 2006). Here, I will first summarize the basic mechanism of membrane protein insertion in the ER and will then review the main results that...