Molecular Mechanism of Sugar Transport by a SWEET Transporter

Abstract

SWEET sugar transporters play critical roles in many physiological processes in plants and animals. They also serve as excellent models for understanding the alternating access transport mechanism. We captured the high-resolution structures of a SWEET family of sugar transporter in three major conformational states, including outward-open, occluded and inward-open conformations by protein engineering and crystallography. Our structure of a glucose bound form provided insights into substrate recognition. Furthermore, through unbiased molecular dynamics simulations, we observed spontaneous transitions from an outward-open to an inward-open state, as well as the accompanying substrate translocation events across the membrane. The unguided computational simulations matched well with the experimental structures. These data, along with functional studies and dynamic characterizations, suggest mechanisms to explain allosteric coupling of gates and transitions between conformational states. These studies lead to atomic level insights into how sugar is translocated across the membrane through an alternating access transporter.