The topology of membrane proteins is determined by:
Topological orientation of membrane proteins, defined by which loops face cytosolic versus exoplasmic or lumenal space, is encoded within polypeptide itself as a set of topogenic signals rather than imposed solely by external receptors. As nascent chain enters Sec61 translocon, hydrophobic segments can function either as start-transfer signal-anchor that opens lateral gate and initiates translocation of downstream region, or as stop-transfer sequence that halts translocation and partitions laterally into lipid bilayer through same gate formed by helices 2b and 7. Positive-inside rule, first do
Ref: von Heijne G, Annu Rev Biophys 36: 2007, Membrane Protein Topology Determinants.
