Structure and function of SemiSWEET and SWEET sugar transporters

• SemiSWEETs and SWEETs are sugar transporters present in all kingdoms of life.
• SWEETs serve critical roles in sugar allocation in plants.
• Physiological roles in plants predominantly relate to cellular efflux.
• Bacterial SemiSWEETs, among the smallest known transporters, are built from a polypeptide comprising a triple helix bundle.
• The minimal functional unit of the SemiSWEETs is a dimer.
• SemiSWEETs have been crystallized in three states: outward open, occluded, and inward open.
• The eukaryotic SWEETs comprise a duplicated triple helix bundle connected via an inversion linker helix.

SemiSWEETs and SWEETs have emerged as unique sugar transporters. First discovered in plants with the help of fluorescent biosensors, homologs exist in all kingdoms of life. Bacterial and plant homologs transport hexoses and sucrose, whereas animal SWEETs transport glucose. Prokaryotic SemiSWEETs are small and comprise a parallel homodimer of an approximately 100 amino acid-long triple helix bundle (THB). Duplicated THBs are fused to create eukaryotic SWEETs in a parallel orientation via an inversion linker helix, producing a similar configuration to that of SemiSWEET dimers. Structures of four SemiSWEETs have been resolved in three states: open outside, occluded, and open inside, indicating alternating access. As we discuss here, these atomic structures provide a basis for exploring the evolution of structure–function relations in this new class of transporters.