Structures of bacterial homologues of SWEET transporters in two distinct conformations.

TitleStructures of bacterial homologues of SWEET transporters in two distinct conformations.
Publication TypeJournal Article
Year of Publication2014
AuthorsXu, Y, Tao, Y, Cheung, LS, Fan, C, Chen, L-Q, Xu, S, Perry, K, Frommer, WB, Feng, L
JournalNature
Volume515
Issue7527
Pagination448-52
Date Published2014 Nov 20
ISSN1476-4687
KeywordsArabidopsis, Bacterial Proteins, Crystallography, X-Ray, Evolution, Molecular, Glucose, Leptospira, Models, Molecular, Monosaccharide Transport Proteins, Movement, Protein Conformation, Protein Multimerization, Structure-Activity Relationship, Vibrio
Abstract

SWEETs and their prokaryotic homologues are monosaccharide and disaccharide transporters that are present from Archaea to plants and humans. SWEETs play crucial roles in cellular sugar efflux processes: that is, in phloem loading, pollen nutrition and nectar secretion. Their bacterial homologues, which are called SemiSWEETs, are among the smallest known transporters. Here we show that SemiSWEET molecules, which consist of a triple-helix bundle, form symmetrical, parallel dimers, thereby generating the translocation pathway. Two SemiSWEET isoforms were crystallized, one in an apparently open state and one in an occluded state, indicating that SemiSWEETs and SWEETs are transporters that undergo rocking-type movements during the transport cycle. The topology of the triple-helix bundle is similar yet distinct to that of the basic building block of animal and plant major facilitator superfamily (MFS) transporters (for example, GLUTs and SUTs). This finding indicates two possibilities: that SWEETs and MFS transporters evolved from an ancestral triple-helix bundle or that the triple-helix bundle represents convergent evolution. In SemiSWEETs and SWEETs, two triple-helix bundles are arranged in a parallel configuration to produce the 6- and 6 + 1-transmembrane-helix pores, respectively. In the 12-transmembrane-helix MFS transporters, four triple-helix bundles are arranged into an alternating antiparallel configuration, resulting in a much larger 2 × 2 triple-helix bundle forming the pore. Given the similarity of SemiSWEETs and SWEETs to PQ-loop amino acid transporters and to mitochondrial pyruvate carriers (MPCs), the structures characterized here may also be relevant to other transporters in the MtN3 clan. The insight gained from the structures of these transporters and from the analysis of mutations of conserved residues will improve the understanding of the transport mechanism, as well as allow comparative studies of the different superfamilies involved in sugar transport and the evolution of transporters in general.

DOI10.1038/nature13670
Alternate JournalNature
Citation Key10.1038/nature13670
PubMed ID25186729
PubMed Central IDPMC4300204
Grant ListP41 GM103403 / GM / NIGMS NIH HHS / United States
P41 GM103403 / GM / NIGMS NIH HHS / United States