Orientation of membrane proteins remains fixed

Membrane proteins are thought to attain their unique orientation very early, already when they are being produced. Flipping the pre-set orientations of proteins in the membrane was always believed to be an impossible process. However, recent studies have cast doubt on this view, causing a debate. Now, a paper published in PNAS, instead confirms the prevailing assumption that as a general rule, orientations are determined when the protein is produced and cannot change afterwards.

Cell membranes are crowded with proteins that perform a huge variety of roles, such as transferring nutrients across the membrane, sensing the cell’s environment, transmitting signals into the cell and many more. Membrane proteins sit in the membrane with a pre-set orientation; a receptor protein for example will have the sensing part on the side that points to the outside of the cell, whereas the signaling part will point inwards.

The present study, led by Gunnar von Heijne (Stockholm University/SciLifeLab) followed the orientation of a small membrane protein that can exist in both orientations in the membrane (a very uncommon situation for membrane proteins) over time. The results showed that the protein does not flip its orientation – every protein molecule remains in its early-determined orientation.