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Updated: May 23, 2026
08:14
Determining Membrane Protein Topology Using Fluorescence Protease Protection (FPP)
Published on: April 20, 2015
Undecided membrane proteins insert in random topologies. Up, down and sideways: it does not really matter
1Department of Biological Chemistry, Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, 91904 Jerusalem, Israel. shimon.schuldiner@huji.ac.il
Trends in Biochemical Sciences
|March 27, 2012
Summary
Small multidrug transporters, functioning as dimers, can adopt various membrane topologies (NiCi and NoCo orientations). This flexibility supports a simple transport mechanism driven solely by external forces.
Area of Science:
- Biochemistry
- Molecular Biology
- Membrane Protein Structure
Background:
- Membrane proteins typically require specific topologies for function.
- Small multidrug transporters are crucial for cellular efflux pumps.
Purpose of the Study:
- To investigate the functional topologies of dimeric small multidrug transporters.
- To challenge the assumption of unique topological requirements for membrane protein function.
Main Methods:
- Analysis of dimeric small multidrug transporter structures.
- Functional assays under varying topological conditions (simulated).
Main Results:
- Dimeric small multidrug transporters can function in multiple orientations.
- Both NiCi (cytoplasmic N and C termini) and NoCo (external N and C termini) topologies are functional.
- Transporter function is maintained in both parallel and antiparallel dimeric arrangements.
- Transport directionality is independent of specific protomer orientation.
Conclusions:
- Membrane protein topology is not always rigidly fixed for function.
- Dimeric transporters exhibit remarkable topological plasticity.
- Transport mechanisms can be simplified, relying on driving force rather than fixed orientation.
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