Structural basis for functional interactions in dimers of SLC26 transporters

• Published in: Nature communications 2019-05, Vol.10 (1), p.2032-10, Article 2032
• Main Authors: Chang, Yung-Ning, Jaumann, Eva A., Reichel, Katrin, Hartmann, Julia, Oliver, Dominik, Hummer, Gerhard, Joseph, Benesh, Geertsma, Eric R.
• Format: Article
• Language: English
• Subjects: 631/45/535; 631/45/56; 631/45/612/1222; 82/80; 82/83; 96/35; Bacterial Proteins - chemistry; Bacterial Proteins - genetics; Bacterial Proteins - isolation & purification; Bacterial Proteins - metabolism; Computer simulation; Deinococcus; Dimerization; Dimers; Distance measurement; Electron Spin Resonance Spectroscopy; Humanities and Social Sciences; Inverted repeat; Lipids; Molecular Dynamics Simulation; Molecular structure; multidisciplinary; Mutagenesis, Site-Directed; Organic Anion Transporters, Sodium-Dependent - chemistry; Organic Anion Transporters, Sodium-Dependent - metabolism; Protein Multimerization; Protein Structure, Quaternary; Recombinant Proteins - chemistry; Recombinant Proteins - genetics; Recombinant Proteins - isolation & purification; Recombinant Proteins - metabolism; Science; Science (multidisciplinary); SLC4A Proteins - chemistry; SLC4A Proteins - metabolism; Structure-function relationships; Sulfate Transporters - chemistry; Sulfate Transporters - genetics; Sulfate Transporters - isolation & purification; Sulfate Transporters - metabolism
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-10001-w

The SLC26 family of transporters maintains anion equilibria in all kingdoms of life. The family shares a 7 + 7 transmembrane segments inverted repeat architecture with the SLC4 and SLC23 families, but holds a regulatory STAS domain in addition. While the only experimental SLC26 structure is monomeric, SLC26 proteins form structural and functional dimers in the lipid membrane. Here we resolve the structure of an SLC26 dimer embedded in a lipid membrane and characterize its functional relevance by combining PELDOR/DEER distance measurements and biochemical studies with MD simulations and spin-label ensemble refinement. Our structural model reveals a unique interface different from the SLC4 and SLC23 families. The functionally relevant STAS domain is no prerequisite for dimerization. Characterization of heterodimers indicates that protomers in the dimer functionally interact. The combined structural and functional data define the framework for a mechanistic understanding of functional cooperativity in SLC26 dimers. The SLC26 family of transporters maintains anion equilibria in all kingdoms of life. Here, the authors resolve the structure of an SLC26 dimer embedded in a lipid membrane and characterize it by PELDOR/DEER distance measurements, biochemical studies with MD simulations and spin-label ensemble refinement.