SWEET proteins

The SWEET (Sugar Will be Eventually Exported Transporters) proteins are the most recently discovered family of sugar transporters [1]. They are found in all life forms and exports both mono and di-saccharides down the concentration gradient. With six transmembrane helices, they form a simple architecture of membrane proteins which undergoes transporter mechanism [2].

dbSWEET

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The bioinformatic analysis of protein families helps in identifying their specific features responsible for expression, structure, mechanism, and function. On the other hand, membrane proteins propose various hurdles and are tough for structural investigations.
For SWEET sugar transporters, only inward open eukaryotic and 7 prokaryotic crystal structures (inward-open, occluded, outward-open) have been elucidated till now. dbSWEET is a repository composed of several bioinformatic analysis of SWEET Sugar Transporter family. The database contains various structural, sequence and functional information about this protein family.

We have performed pairwise global sequence alignment of SWEET homologs from different taxanomic groups to obtain average identity between and within the groups. Click here. Because the sequences are very diverse we have proposed a generic numbering scheme for SWEET family of proteins. Click here.

Information Available

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The database contains more than 2000 manually curated structural models of SWEET proteins from bacteria, archaea and eukaryotes.       dbSWEET Statistics

Information Available

  • Manually curated structure based sequence alignment of sequences
  • Structural models of SWEET family members, constructed using homology modeling (Modeler 9.16)
  • Structural comparision and sequence alignments with known PDB structures
  • Gene pattern information
  • Substrate binding site properties
  • Selectivity filter residues and its properties
  • Protein family and function
  • Residue conservation of key positions in SWEET protein family
  • Average pairwise sequence identity of SWEET homologs from prokaryotes and eukaryotes and Generic numbering scheme for SWEET family of proteins

Tools in dbSWEET

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  • Blast search: Blast dbSWEET with query sequence
  • Multiple Sequence Alignment of selected SWEET sequences using CLUSTAL
  • Phylogenetic analysis using Maximum-likelihood and Neighborjoining methods using MEGA

Searching the database

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The Search page provides access to the dbSWEET information. User can enter Uniprot ID, or the amino-acids sequence in the Basic Search dialog box. Advanced Search Options enable filtering data according to the Binding-site residues, kingdoms or organisms. User can also search the the database, with the help of keywords through the Autosearch option. The query result is displayed on the "Results page".

dbSWEET provides BLAST search options, to find potential SWEET homologs corresponding to the query sequence. The user needs to enter only the amino-acid sequence of the query, without any header or formatting. The Blast output provides two links. The "Blast Output" option show Blast-xml result file. The "Hits identified" option leads to tabular display of hits, similar to the "Results page" explained below.

  • Results page
  • The hits corresponding to the query entered are displayed in a tabular format. Each row represents a single Protein entry. Multiple enteries can be selected for further analysis. The View alignment option shows the structure based alignment of transmembrane segments 1-2-3 and 5-6-7, i.e. Triple-Helix-Bundles (THBs) of the selected SWEET sequences. The User can create their own alignment with full length protein sequence of enteries, with the help of Clustal Omega tool provided in dbSWEET. Also the phylogenetic tree can be constructed using the inbuilt MEGA software: Maximum-likelyhood or Neighbor-joining methods can be used. The manually curated MSA containing only transmembrane segments is used as input for phylogeny. The upper limit for MSA and phylogenetic analysis is 100 sequences.
    The protein sequences for selected enteries can be downloaded (in fasta format) using Download sequence option.
    For further information on individual enteries, click on the Details option given at the end of each row.
  • Details page
  • The navigation bar at the left helps to navigate through the information available for every entry. Information like Taxanomic details, Sequence information, binding-site residues characterstics, Gene Information, Gene Ontology data and Protein family is provided on this page. The Modeled structures (and the corresponding alignment files) for all the enteries can be download.

    The Structural Models
    Models in three different conformations (Inward-open, Outward-open and Occluded) have been built by homology modeling, using Modeler9.16 .
    For SWEET proteins from eukaryotes, the Inward-open structures were modeled by using rice SWEET homolog as template (pdb id: 5CTG). The Outward-open and Occluded structures were modeled with the help of Bacterial homologs from E.coli (pdb id: 4X5N, 4RNG and 4QNC).
    For prokaryotic Semi-SWEET homologs, dimers were modeled in the three conformations with the help of crystal structures in Inward-open (pdb id: 4X5M), Outward-open (pdb id: 4X5N) and Occluded (pdb id: 4QNC and 4RNG ) states.

Citing dbSWEET

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If you use dbSWEET in your work, please cite the following article:

dbSWEET: An Integrated Resource for SWEET Superfamily to Understand, Analyze and Predict the Function of Sugar Transporters in Prokaryotes and Eukaryotes. Ankita Gupta, Ramasubbu Sankararamakrishnan. Journal of Molecular Biology, 2018 Apr. 10.1016/j.jmb.2018.04.013

References

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  • Sugar transporters for intercellular exchange and nutrition of pathogens. Chen LQ, Hou BH, Lalonde S, Takanaga H, Hartung ML, Qu XQ, Guo WJ, Kim JG, Underwood W, Chaudhuri B, Chermak D, Antony G, White FF, Somerville SC, Mudgett MB, Frommer WB. Nature, 2010 Nov.Pubmed:21107422
  • Structure of a eukaryotic SWEET transporter in a homotrimeric complex.Yuyong Tao, Lily S. Cheung, Shuo Li, Joon-Seob Eom, Li-Qing Chen, Yan Xu, Kay Perry, Wolf B. Frommer, and Liang Feng. Nature, 2015 Nov.Pubmed:26479032
  • MIPModDB: a central resource for the superfamily of major intrinsic proteins. Anjali B. Gupta, Ravi Kumar Verma, Vatsal Agarwal, Manu Vajpai, Vivek Bansal and Ramasubbu Sankararamakrishnan. Nucleic Acids Research, 2012 Jan.Pubmed:22080560
  • Anion-selective Formate/nitrite transporters: taxonomic distribution, phylogenetic analysis and subfamily-specific conservation pattern in prokaryotes. Mishtu Mukherjee, Manu Vajpai and Ramasubbu Sankararamakrishnan. BMC Genomics, 2017 Jul.Pubmed:28738779
Bioinformatics and Biomolecular Simulation Laboratory, Department of Biological Sciences and Bioengineering, IIT Kanpur