Structural Dynamics and Energetics of Glucose Transport via Rice SWEET Sugar Transporter

Abstract

The transport of sugars across the cell membrane is vital for any living cell on earth. The SWEET sugar transporters are ubiquitously present in all the life forms. Their prevalence and the physiological role are extensively reviewed in plants, where they can selectively transport mono- and disaccharides down the concentration gradient. They mediate functions crucial for plant growth and development. The functional aspects of metazoan SWEET homologs remain unclear. The SWEET domain comprises three transmembrane helices or a triple-helix-bundle (THB). in prokaryotes, two such THBs dimerize to form a functional pore, whereas, in eukaryotes, two THBs are fused with a linker-helix. The crystal structures of bacterial SWEET homologs are available in inward-open, occluded, and outward-open conformations. The eukaryotic SWEET homolog is crystallized only in inward-open conformation. Structural studies thus suggest transport via the alternating-access-transport mechanism. The understanding of the structural dynamics and energetics of substrate transport through SWEET transporters is limited. Earlier, we have compiled our exhaustive curation of SWEET homologs in dbSWEET database and investigated the substrate-selectivity mechanism of rice SWEET homolog (OsSWEET2b). in this study, we investigated the structural features stabilizing the three conformational states of OsSWEET2b using simulation studies. We have evaluated the PMF profiles of glucose transport in all three conformational states and arrived at an integrated profile. The maximum energy barrier for glucose transport from the extracellular side to the cytoplasmic side is 22kJ/mol. We identified two transition states - T1 (transition from outward-open to occluded state) and T2 (transition from occluded state to inward-open state), and the residues responsible for these conformational-transitions. This study highlights the key features responsible for structural transitions mediated by glucose transport through eukaryotic SWEET homolog.