Stable membrane orientations of small dual-topology membrane proteins

Significance The orientations of multispanning membrane proteins in the membrane are initially determined when they are cotranslationally inserted into the membrane. However, it is not always clear whether these initial orientations may be dynamic after the insertion step or not. The present study shows that even in the case of small membrane proteins that have only four transmembrane helices and have little bias to be inserted in one or the other orientation, the initially inserted orientation remains stable and is not dynamic, at least with respect to the orientation of the entire protein. This finding suggests that membrane proteins become correctly oriented already during or immediately after synthesis, as they are inserted into the membrane.