Undecided membrane proteins insert in random topologies. Up, down and sideways: it does not really matter
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Updated: May 23, 2026

Determining Membrane Protein Topology Using Fluorescence Protease Protection (FPP)
Published on: April 20, 2015
1Department of Biological Chemistry, Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, 91904 Jerusalem, Israel. shimon.schuldiner@huji.ac.il
Abstract:
It is usually assumed that to ensure proper function, membrane proteins must be inserted in a unique topology. However, a number of dimeric small multidrug transporters can function in the membrane in various topologies. Thus, the dimers can be a random mixture of NiCi (N and C termini facing the cell cytoplasm) and NoCo (N and C termini facing the outside) orientation. In addition, the dimer functions whether the two protomers are parallel (N and C termini of both protomers on the same side of the membrane) or antiparallel (N and C termini of each protomer on opposite sides of the membrane). This unique phenomenon provides strong support for a simple mechanism of transport where the directionality is determined solely by the driving force.
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