Structure and function of SemiSWEET and SWEET sugar transporters

doi:10.1016/j.tibs.2015.05.005

Trends in Biochemical Sciences

Volume 40, Issue 8, August 2015, Pages 480-486

https://doi.org/10.1016/j.tibs.2015.05.005 Get rights and content

Highlights

•
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.

Section snippets

SWEETs and sugar transport

Living organisms depend on soluble sugars as the major source of carbon skeletons and energy. Organisms have found ways to facilitate the passage of sugars across cellular membranes and to control sugar influx and efflux depending on their supply and demand. Over the past 20 years, many key sugar transporters have been identified from bacteria, fungi, plants, and humans [1]. These transporters can be categorized into four superfamilies: bacterial phosphotransferase (PTS) systems, ATP-binding

Important physiological roles of SWEETs in plants

Plant genomes typically contain approximately 20 SWEET paralogs, which are differentially expressed, implicating them in a range of sugar translocation steps. Arabidopsis SWEETs fall into four subclades and share 27–80% identity. Clades I, II, and IV appear to be predominantly hexose transporters, whereas clade III SWEETs transport predominantly sucrose, although some also can transport hexoses. SWEETs can localize to different cellular compartments, in particular the plasma membrane (e.g.,

Physiological role of SWEETs in animals and humans

To date, and despite the apparent potential for affecting sugar homeostasis in animals and humans, little is known about the physiological role of SWEETs in animals. Although animal genomes, including that of humans, typically contain only a single SWEET gene, a major exception is Caenorhabditis elegans, which contains seven SWEET paralogs. Both the human and one of the C. elegans SWEETs mediate glucose transport. Their broad expression patterns implicate them as fundamental sugar transporters

SemiSWEET structures

Recent breakthroughs in the structural determination of four SemiSWEET homologs revealed the architecture of SemiSWEET, captured three conformational states, and provided rich structural insights into the transport mechanism of these transporters 10, 11, 22.

This burst of structures started in 2014, when VsSemiSWEET (from Vibrio sp. N418) and LbSemiSWEET were determined at 1.7-Å and 2.4-Å resolution, respectively [10]. VsSemiSWEET was found to be in an outward open state, while LbSemiSWEET was

Transport pathway and putative substrate binding pockets of SemiSWEETs

A fundamental question about any particular transporter is how it forms a selective transport route for its substrates within the membrane. The availability of four SemiSWEET structures enables the identification and close examination of the transport pathway that is formed around the twofold axis of symmetry. The transport route is shielded by TMs from the membrane and only accessible either from the extracellular side in the outward open state or from the intracellular side in the inward open

Conformation states and the transport cycle

SemiSWEET structures in different conformational states are fully compatible with an alternating access model 10, 11, 22, in which the substrate-binding pocket alternatively exposes to either side of the membrane. VsSemiSWEET and one form of EcSemiSWEET were captured in an outward open formation, with a large solvent access route from the extracellular surface all the way to the putative substrate-binding pocket. LbSemiSWEET and TySemiSWEET were crystalized in an occluded state, with a cavity

Concluding remarks

The recent identification and functional characterization of SWEET proteins and structural elucidation of their bacterial homologs, SemiSWEETs, have greatly advanced our understanding of the function and transport mechanisms of this important protein family. Despite this rapid progress, many questions remain regarding their transport cycle, transport mechanism, and physiological roles, especially of bacterial and animal SWEETs (Box 1).

A first question is what drives the conformational

Acknowledgments

Original research has been supported by grants from the Department of Energy (DE-FG02-04ER15542), the National Science Foundation (IOS-1258018), and the Bill and Melinda Gates Foundation to W.B.F, and by Stanford University, the Harold and Leila Y. Mathers Charitable Foundation, and Alfred P. Sloan Foundation to L.F. We thank Frommer lab members and Feng lab members for stimulating discussions.

References (33)

J.S. Eom
SWEETs, transporters for intracellular and intercellular sugar translocation
Curr. Opin. Plant Biol.
(2015)
F. Chardon
Leaf fructose content is controlled by the vacuolar transporter SWEET17 in Arabidopsis
Curr. Biol.
(2013)
N. Yan
Structural advances for the major facilitator superfamily (MFS) transporters
Trends Biochem. Sci.
(2013)
M. Hamada
Ci-Rga, a gene encoding an MtN3/saliva family transmembrane protein, is essential for tissue differentiation during embryogenesis of the ascidian Ciona intestinalis
Differentiation
(2005)
L-Q. Chen
Transport of sugars
Annu. Rev. Biochem.
(2015)
V. Chaptal
Crystal structure of lactose permease in complex with an affinity inactivator yields unique insight into sugar recognition
Proc. Natl. Acad. Sci. U.S.A.
(2011)
E.M. Wright
Biology of human sodium glucose transporters
Physiol. Rev.
(2011)
L.Q. Chen
Sugar transporters for intercellular exchange and nutrition of pathogens
Nature
(2010)
L.Q. Chen
Sucrose efflux mediated by SWEET proteins as a key step for phloem transport
Science
(2012)
L.Q. Chen
Embryo nutrition by a cascade of sequentially expressed sucrose transporters in the seed coat
Plant Cell
(2015)

I.W. Lin

Nectar secretion requires sucrose phosphate synthases and the sugar transporter SWEET9

Nature

(2014)

Y.H. Xuan

Functional role of oligomerization for bacterial and plant SWEET sugar transporter family

Proc. Natl. Acad. Sci. U.S.A.

(2013)

Y. Xu

Structures of bacterial homologues of SWEET transporters in two distinct conformations

Nature

(2014)

Y. Lee

Structural basis for the facilitative diffusion mechanism by SemiSWEET transporter

Nat. Commun.

(2015)

Y.F. Guan

RUPTURED POLLEN GRAIN1, a member of the MtN3/saliva gene family, is crucial for exine pattern formation and cell integrity of microspores in Arabidopsis

Plant Physiol.

(2008)

P.J. Seo

An Arabidopsis senescence-associated protein SAG29 regulates cell viability under high salinity

Planta

(2011)

Cited by (121)

Sugar transporters spatially organize microbiota colonization along the longitudinal root axis of Arabidopsis
2024, Cell Host and Microbe
Plant roots are functionally heterogeneous in cellular architecture, transcriptome profile, metabolic state, and microbial immunity. We hypothesized that axial differentiation may also impact spatial colonization by root microbiota along the root axis. We developed two growth systems, ArtSoil and CD-Rhizotron, to grow and then dissect Arabidopsis thaliana roots into three segments. We demonstrate that distinct endospheric and rhizosphere bacterial communities colonize the segments, supporting the hypothesis of microbiota differentiation along the axis. Root metabolite profiling of each segment reveals differential metabolite enrichment and specificity. Bioinformatic analyses and GUS histochemistry indicate microbe-induced accumulation of SWEET2, 4, and 12 sugar uniporters. Profiling of root segments from sweet mutants shows altered spatial metabolic profiles and reorganization of endospheric root microbiota. This work reveals the interdependency between root metabolites and microbial colonization and the contribution of SWEETs to spatial diversity and stability of microbial ecosystem.
Structure, evolution, and roles of SWEET proteins in growth and stress responses in plants
2024, International Journal of Biological Macromolecules
Carbohydrates are exported by the SWEET family of transporters, which is a novel class of carriers that can transport sugars across cell membranes and facilitate sugar's long-distance transport from source to sink organs in plants. SWEETs play crucial roles in a wide range of physiologically important processes by regulating apoplastic and symplastic sugar concentrations. These processes include host-pathogen interactions, abiotic stress responses, and plant growth and development. In the present review, we (i) describe the structure and organization of SWEETs in the cell membrane, (ii) discuss the roles of SWEETs in sugar loading and unloading processes, (iii) identify the distinct functions of SWEETs in regulating plant growth and development including flower, fruit, and seed development, (iv) shed light on the importance of SWEETs in modulating abiotic stress resistance, and (v) describe the role of SWEET genes during plant-pathogen interaction. Finally, several perspectives regarding future investigations for improving the understanding of sugar-mediated plant defenses are proposed.
Glucose transport, transporters and metabolism in diabetic retinopathy
2024, Biochimica et Biophysica Acta - Molecular Basis of Disease
Diabetic retinopathy (DR) is the most common reason for blindness in working-age individuals globally. Prolonged high blood glucose is a main causative factor for DR development, and glucose transport is prerequisite for the disturbances in DR caused by hyperglycemia. Glucose transport is mediated by its transporters, including the facilitated transporters (glucose transporter, GLUTs), the “active” glucose transporters (sodium-dependent glucose transporters, SGLTs), and the SLC50 family of uniporters (sugars will eventually be exported transporters, SWEETs). Glucose transport across the blood-retinal barrier (BRB) is crucial for nourishing the neuronal retina in the context of retinal physiology. This physiological process primarily relies on GLUTs and SGLTs, which mediate the glucose transportation across both the cell membrane of retinal capillary endothelial cells and the retinal pigment epithelium (RPE). Under diabetic conditions, increased accumulation of extracellular glucose enhances the retinal cellular glucose uptake and metabolism via both glycolysis and glycolytic side branches, which activates several biochemical pathways, including the protein kinase C (PKC), advanced glycation end-products (AGEs), polyol pathway and hexosamine biosynthetic pathway (HBP). These activated biochemical pathways further increase the production of reactive oxygen species (ROS), leading to oxidative stress and activation of Poly (ADP-ribose) polymerase (PARP). The activated PARP further affects all the cellular components in the retina, and finally resulting in microangiopathy, neurodegeneration and low-to-moderate grade inflammation in DR. This review aims to discuss the changes of glucose transport, glucose transporters, as well as its metabolism in DR, which influences the retinal neurovascular unit (NVU) and implies the possible therapeutic strategies for treating DR.
Involvement of plant signaling network and cell metabolic homeostasis in nitrogen deficiency-induced early leaf senescence
2023, Plant Science
Nitrogen (N) is a basic building block that plays an essential role in the maintenance of normal plant growth and its metabolic functions through complex regulatory networks. Such the N metabolic network comprises a series of transcription factors (TFs), with the coordinated actions of phytohormone and sugar signaling to sustain cell homeostasis. The fluctuating N concentration in plant tissues alters the sensitivity of several signaling pathways to stressful environments and regulates the senescent-associated changes in cellular structure and metabolic process. Here, we review recent advances in the interaction between N assimilation and carbon metabolism in response to N deficiency and its regulation to the nutrient remobilization from source to sink during leaf senescence. The regulatory networks of N and sugar signaling for N deficiency-induced leaf senescence is further discussed to explain the effects of N deficiency on chloroplast disassembly, reactive oxygen species (ROS) burst, asparagine metabolism, sugar transport, autophagy process, Ca²⁺ signaling, circadian clock response, brassinazole-resistant 1 (BZRI), and other stress cell signaling. A comprehensive understanding for the metabolic mechanism and regulatory network underlying N deficiency-induced leaf senescence may provide a theoretical guide to optimize the source-sink relationship during grain filling for the achievement of high yield by a selection of crop cultivars with the properly prolonged lifespan of functional leaves and/or by appropriate agronomic managements.
A chromosome-level genome assembly for Erianthus fulvus provides insights into its biofuel potential and facilitates breeding for improvement of sugarcane
2023, Plant Communications
Erianthus produces substantial biomass, exhibits a good Brix value, and shows wide environmental adaptability, making it a potential biofuel plant. In contrast to closely related sorghum and sugarcane, Erianthus can grow in degraded soils, thus releasing pressure on agricultural lands used for biofuel production. However, the lack of genomic resources for Erianthus hinders its genetic improvement, thus limiting its potential for biofuel production. In the present study, we generated a chromosome-scale reference genome for Erianthus fulvus Nees. The genome size estimated by flow cytometry was 937 Mb, and the assembled genome size was 902 Mb, covering 96.26% of the estimated genome size. A total of 35 065 protein-coding genes were predicted, and 67.89% of the genome was found to be repetitive. A recent whole-genome duplication occurred approximately 74.10 million years ago in the E. fulvus genome. Phylogenetic analysis showed that E. fulvus is evolutionarily closer to S. spontaneum and diverged after S. bicolor. Three of the 10 chromosomes of E. fulvus formed through rearrangements of ancestral chromosomes. Phylogenetic reconstruction of the Saccharum complex revealed a polyphyletic origin of the complex and a sister relationship of E. fulvus with Saccharum sp., excluding S. arundinaceum. On the basis of the four amino acid residues that provide substrate specificity, the E. fulvus SWEET proteins were classified as mono- and disaccharide sugar transporters. Ortho-QTL genes identified for 10 biofuel-related traits may aid in the rapid screening of E. fulvus populations to enhance breeding programs for improved biofuel production. The results of this study provide valuable insights for breeding programs aimed at improving biofuel production in E. fulvus and enhancing sugarcane introgression programs.
Sequence analysis of SWEET transporters from trypanosomatids and evaluation of its expression in Trypanosoma cruzi
2023, Experimental Parasitology
Trypanosoma cruzi is an obligate parasite that uses glucose as one of the main resources to maintain its survival and proliferation. In eukaryotic cells glucose transport across membranes is mediated by facilitated transport through a variety of transporters. Herein, genes from the recently described SWEET family of carbohydrate transporters were identified in trypanosomatid parasites, including the medically important species T. cruzi and Leishmania spp. The identified genes have sequences with the typical attributes of known SWEET transporters. The expression of TcSWEET, the gene for the SWEET transporter found in the T. cruzi genome, was evidenced by immunohistochemistry using a polyclonal serum raised against peptides selected from the deduced TcSWEET protein sequence. In Western blot analysis, this α-TcSWEET serum detected proteins within the theoretical molecular mass for TcSWEET (25.8 kDa) in total epimastigote lysates, suggesting its expression at this parasite stage. Additionally, this serum stained epimastigotes at localizations consistent with the cell body and the flagellum. Together, these data suggests that SWEET transporters may contribute to glucose transport in trypanosomatid parasites.

View all citing articles on Scopus

View full text

Trends in Biochemical Sciences

ReviewStructure and function of SemiSWEET and SWEET sugar transporters

Highlights

Section snippets

SWEETs and sugar transport

Important physiological roles of SWEETs in plants

Physiological role of SWEETs in animals and humans

SemiSWEET structures

Transport pathway and putative substrate binding pockets of SemiSWEETs

Conformation states and the transport cycle

Concluding remarks

Acknowledgments

Curr. Opin. Plant Biol.

Curr. Biol.

Trends Biochem. Sci.

Differentiation

Transport of sugars

Annu. Rev. Biochem.

Crystal structure of lactose permease in complex with an affinity inactivator yields unique insight into sugar recognition

Proc. Natl. Acad. Sci. U.S.A.

Biology of human sodium glucose transporters

Physiol. Rev.

Sugar transporters for intercellular exchange and nutrition of pathogens

Nature

Sucrose efflux mediated by SWEET proteins as a key step for phloem transport

Science

Embryo nutrition by a cascade of sequentially expressed sucrose transporters in the seed coat

Plant Cell

Nectar secretion requires sucrose phosphate synthases and the sugar transporter SWEET9

Nature

Functional role of oligomerization for bacterial and plant SWEET sugar transporter family

Proc. Natl. Acad. Sci. U.S.A.

Structures of bacterial homologues of SWEET transporters in two distinct conformations

Nature

Structural basis for the facilitative diffusion mechanism by SemiSWEET transporter

Nat. Commun.

RUPTURED POLLEN GRAIN1, a member of the MtN3/saliva gene family, is crucial for exine pattern formation and cell integrity of microspores in Arabidopsis

Plant Physiol.

An Arabidopsis senescence-associated protein SAG29 regulates cell viability under high salinity

Planta

Review
Structure and function of SemiSWEET and SWEET sugar transporters