PZ – Nanobodies for multilevel examination of SLC26 transporters

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Antibodies are indispensable research tools for the detection and manipulation of proteins. However, high quality antibodies with the desired specificity and affinity for SLC26 proteins are currently not available. This is typical for many membrane proteins and is thought to be a direct consequence of poor protein stability, the embedding in lipophilic membrane and their compact size, providing only limited potential epitopes for conventional antibodies. Nanobodies, the variable domain of single-domain antibodies from camelids, offer a promising and proven alternative to conventional antibodies for targeting membrane proteins. Nanobodies are small but fully functional antigen binding fragments that are easily renewed by production in E. coli. Due to a particularly long hypervariable loop, nanobodies can bind into protein cavities, such as the binding clefts in SLC26 carriers. As a result, nanobodies are highly suited to functionally arrest or inhibit these transport proteins for functional and structural studies or use as therapeutics. Furthermore, their small size results in a much better tissue penetration compared to conventional antibodies. We will generate nanobodies against all SLC26 isoform studied in this Research Unit and tailored towards the specific needs of each individual project. The unique ability of nanobodies to target solute carriers, such as the SLC26 proteins, combined with the high versatility in their applications makes them ideal research tools for reaching the versatile goals of this Research Unit ranging from structure determination and protein complex isolation to cellular localization studies and opens the path towards developing therapeutics.