Membrane Protein Insertion: The Biology–Physics Nexus

Membrane proteins are a greasy lot. Thrown into water without detergents, they form intractable aggregates, which minimize exposure of their nonpolar transmembrane surfaces to water. Aggregation would be their certain fate if membrane proteins were translated on the ribosome in the manner of soluble proteins. But this fate is avoided: the elongating polypeptide segment from the ribosome exit tunnel (Voss et al., 2006) passes into the membrane-dwelling translocon assembly whose architecture permits selected segments to enter the membrane bilayer to become transmembrane (TM) helices (for review see White and von Heijne, 2004, 2005; von Heijne, 2006). The principles underlying this selection process are beginning to emerge from our recent studies of the recognition of transmembrane helices by the ER translocon (Hessa et al., 2005a; Meindl-Beinker et al., 2006). As Gunnar von Heijne discusses in his Perspective (p....