title: Structure of a eukaryotic SWEET transporter in a homotrimeric complex.
abstract: Eukaryotes rely on efficient distribution of energy and carbon skeletons between organs in the form of sugars. Glucose in animals and sucrose in plants serve as the dominant distribution forms. Cellular sugar uptake and release require vesicular and/or plasma membrane transport proteins. Humans and plants use proteins from three superfamilies for sugar translocation: the major facilitator superfamily (MFS), the sodium solute symporter family (SSF; only in the animal kingdom), and SWEETs. SWEETs carry mono- and disaccharides across vacuolar or plasma membranes. Plant SWEETs play key roles in sugar translocation between compartments, cells, and organs, notably in nectar secretion, phloem loading for long distance translocation, pollen nutrition, and seed filling. Plant SWEETs cause pathogen susceptibility possibly by sugar leakage from infected cells. The vacuolar Arabidopsis thaliana AtSWEET2 sequesters sugars in root vacuoles; loss-of-function mutants show increased susceptibility to Pythium infection. Here we show that its orthologue, the vacuolar glucose transporter OsSWEET2b from rice (Oryza sativa), consists of an asymmetrical pair of triple-helix bundles, connected by an inversion linker transmembrane helix (TM4) to create the translocation pathway. Structural and biochemical analyses show OsSWEET2b in an apparent inward (cytosolic) open state forming homomeric trimers. TM4 tightly interacts with the first triple-helix bundle within a protomer and mediates key contacts among protomers. Structure-guided mutagenesis of the close paralogue SWEET1 from Arabidopsis identified key residues in substrate translocation and protomer crosstalk. Insights into the structure-function relationship of SWEETs are valuable for understanding the transport mechanism of eukaryotic SWEETs and may be useful for engineering sugar flux.
authors.affiliation: Department of Molecular and Cellular Physiology, 279 Campus Drive, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Yuyong
authors.initials: Y
authors.lastname: Tao
authors.affiliation: Carnegie Institution for Science, Department of Plant Biology, 260 Panama St., Stanford, CA 94305, USA.
authors.forename: Lily S
authors.initials: LS
authors.lastname: Cheung
authors.affiliation: Department of Molecular and Cellular Physiology, 279 Campus Drive, Stanford University School of Medicine, Stanford, CA 94305, USA.|Center of Growth, Metabolism and Aging, Key Laboratory of Bio-Resource and Eco-Environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, 610014, China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Li
authors.affiliation: Carnegie Institution for Science, Department of Plant Biology, 260 Panama St., Stanford, CA 94305, USA.
authors.forename: Joon-Seob
authors.initials: JS
authors.lastname: Eom
authors.affiliation: Carnegie Institution for Science, Department of Plant Biology, 260 Panama St., Stanford, CA 94305, USA.
authors.forename: Li-Qing
authors.initials: LQ
authors.lastname: Chen
authors.affiliation: Department of Molecular and Cellular Physiology, 279 Campus Drive, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: NE-CAT and Dep. of Chemistry and Chemical Biology, Cornell University, Building 436E, Argonne National Laboratory, 9700 S. Cass Avenue, Argonne, IL 60439, USA.
authors.forename: Kay
authors.initials: K
authors.lastname: Perry
authors.affiliation: Carnegie Institution for Science, Department of Plant Biology, 260 Panama St., Stanford, CA 94305, USA.
authors.forename: Wolf B
authors.initials: WB
authors.lastname: Frommer
authors.affiliation: Department of Molecular and Cellular Physiology, 279 Campus Drive, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: Feng
mesh_terms: D017360:Arabidopsis / Q000737:chemistry; D029681:Arabidopsis Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001692:Biological Transport; D018360:Crystallography, X-Ray; D051246:Glucose Transport Proteins, Facilitative / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D008958:Models, Molecular; D009004:Monosaccharide Transport Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012275:Oryza / Q000737:chemistry* / Q000235:genetics; D052585:Phloem; D010940:Plant Proteins / Q000737:chemistry* / Q000378:metabolism; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D013329:Structure-Activity Relationship
chemical_list: D029681:Arabidopsis Proteins; D051246:Glucose Transport Proteins, Facilitative; D009004:Monosaccharide Transport Proteins; D010940:Plant Proteins; C000603343:SWEET1 protein, Arabidopsis