Formation of cytoplasmic turns between two closely spaced transmembrane helices during membrane protein integration into the ER membrane

The helical hairpin, two closely spaced transmembrane helices separated by a short turn, is a recurring structural element in integral membrane protei ns, and may serve as a compact unit that inserts into the membrane En bloc. Previously, we have determined the propensities of the 20 natural amino ac ids, when present in the middle of a long hydrophobic stretch, to induce th e formation of a helical hairpin with a lumenally exposed turn during membr ane protein assembly into the endoplasmic reticulum membrane. Here, we pres ent results from a similar set of measurements, but with the turn placed on the cytoplasmic side of the membrane. We find that a significantly higher number of turn-promoting residues need to be present to induce a cytoplasmi c turn compared to a lumenal turn, and that, in contrast to the lumenal tur n, the positively charged residues Arg and Lys are the strongest turn-promo ters in cytoplasmic turns. These results suggest that the process of turn f ormation between transmembrane helices is different for lumenal and cytopla smic turns. (C) 2000 Academic Press.