Conformational change category listing 1 | Beckstein Lab

NHE9 is a sodium/proton exchanger in mammals, part of a large family of secondary active transporters. Our collaborators (David Drew at the University of Stockholm) solved the structure of NHE9 (SLC9A9) from horse with cryo electron-microscopy to 3.2 Å resolution in an inward facing conformation, the first structure of a mammalian sodium/proton antiporter. Functional measurements, structural bioinformatics, and MD simulations all indicate that many components of the transport mechanism are similar between prokaryotic and mammalian sodium/proton antiporters.

Transport of ions and small molecules across the cell membrane against electrochemical gradients is catalyzed by integral membrane proteins that use a source of free energy to drive the energetically uphill flux of the transported substrate. Here we review general principles that apply to most secondary active transporters, namely energy coupling through kinetic cycles and the thermodynamic driving forces, inverted repeat symmetry as a means to generate bi-stable systems that can function according to the alternating access model, and understanding transporters as gated pores.

Bor1p is a secondary transporter in yeast that is responsible for boron transport, likely powered by the proton gradient across the cell membrane. By combining cryo-electron microscopy and MD simulations we could generate models of Bor1p in inward facing and outward facing conformation, which suggest rigid body movements of the core domain relative to the gate domain, consistent with a rocking-bundle transport mechanism.