RT Journal Article
SR Electronic
T1 Structural basis for functional interactions in dimers of SLC26 transporters
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 518209
DO 10.1101/518209
A1 Yung-Ning Chang
A1 Eva A. Jaumann
A1 Katrin Reichel
A1 Julia Hartmann
A1 Dominik Oliver
A1 Gerhard Hummer
A1 Benesh Joseph
A1 Eric R. Geertsma
YR 2019
UL http://biorxiv.org/content/early/2019/01/11/518209.abstract
AB 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 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 exerts a stabilizing effect on regions central in this dimer. 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.