Transporter oligomerization: form and function.

Yilmaz Alguel,George Diallinas,Bernadette Byrne,Alexander D Cameron

doi:10.1042/bst20160217

Yilmaz Alguel, George Diallinas + Show 2 more

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https://doi.org/10.1042/bst20160217

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Transporters are integral membrane proteins with central roles in the efficient movement of molecules across biological membranes. Many transporters exist as oligomers in the membrane. Depending on the individual transport protein, oligomerization can have roles in membrane trafficking, function, regulation and turnover. For example, our recent studies on UapA, a nucleobase ascorbate transporter, from Aspergillus nidulans, have revealed both that dimerization of this protein is essential for correct trafficking to the membrane and the structural basis of how one UapA protomer can affect the function of the closely associated adjacent protomer. Here, we review the roles of oligomerization in many particularly well-studied transporters and transporter families.

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The formation of transporter oligomers has been studied by a range of methods, including fluorescence resonance energy transfer (FRET) [1], cross-linking [2], pull-downs [3] and co-immunoprecipitation [4], as well as biophysical characterization using, for example, size-exclusion chromatography–multiangle light scattering (SEC–MALS) [5]
It should be noted that in the case of the sodium–proton antiporter, NapA, the dimer interface is very similar in the crystal structures of both the inward- and outward-facing conformations [18,19], it is not clear whether dimerization is important for function in this protein
It is possible that the lack of conformational change in one protomer inhibits movement in associated molecules. These findings strongly suggest that SWEET homotrimers function through co-operativity between protomers; the precise molecular basis of this is yet to be revealed

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Introduction

The formation of transporter oligomers has been studied by a range of methods, including fluorescence resonance energy transfer (FRET) [1], cross-linking [2], pull-downs [3] and co-immunoprecipitation [4], as well as biophysical characterization using, for example, size-exclusion chromatography–multiangle light scattering (SEC–MALS) [5]. While such approaches have effectively shown the formation of transporter oligomers, more recent investigations using dominant mutants and high-resolution structural studies have started revealing insights into the precise roles of oligomerization for transporter trafficking, function and regulation of function. There are additional examples where high-resolution structures have revealed that the interface between transporter protomers in an oligomeric arrangement forms the substrate-binding site and translocation channel.

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