A new class of binding-protein dependent solute transporter exemplified by the TAXI-GltS system from Bordetella pertussis

Abstract Tripartite ATP-independent periplasmic (TRAP) transporters are widespread in prokaryotes, but absent in eukaryotes, and transport various substrates. TRAP transporters are typically composed of a monomeric substrate binding protein (SBP) and a characteristic transmembrane component. Here, w...

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Main Authors: Lily M. Jaques, Joseph F. S. Davies, Jack J. Sheldon-Towler, David J. Kelly, Vanessa Leone, Christopher Mulligan
Format: Article
Language:English
Published: Nature Portfolio 2025-08-01
Series:Communications Biology
Online Access:https://doi.org/10.1038/s42003-025-08591-x
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author Lily M. Jaques
Joseph F. S. Davies
Jack J. Sheldon-Towler
David J. Kelly
Vanessa Leone
Christopher Mulligan
author_facet Lily M. Jaques
Joseph F. S. Davies
Jack J. Sheldon-Towler
David J. Kelly
Vanessa Leone
Christopher Mulligan
author_sort Lily M. Jaques
collection DOAJ
description Abstract Tripartite ATP-independent periplasmic (TRAP) transporters are widespread in prokaryotes, but absent in eukaryotes, and transport various substrates. TRAP transporters are typically composed of a monomeric substrate binding protein (SBP) and a characteristic transmembrane component. Here, we describe the discovery and characterisation of a TRAP SBP from the TAXI subfamily with a previously unidentified architecture. BP0403 from Bordetella pertussis is a predicted lipoprotein with 3 distinct domains; an α/β globular domain, a helical domain and a C-terminal TAXI SBP domain. Characterisation of full-length BP0403 reveals that it forms a stable dimer, and structural modelling coupled with molecular weight analysis reveals that the interdomain helical region is solely responsible for dimerisation. Differential scanning fluorimetry (DSF) and intrinsic tyrosine fluorescence reveal that BP0403 binds L-glutamate with nanomolar affinity. Unexpectedly, genome context analysis of BP0403 reveals no TRAP membrane component genes; instead, we find co-localisation and translational coupling with gltS, encoding a Na+/glutamate symporter. In other bacteria, we identified fused BP0403-GltS homologues, strongly suggesting that this constitutes a completely novel SBP-dependent secondary active transporter. Structural comparisons suggest GltS operates by an elevator-type mechanism, like TRAP transporters; the association of an SBP with this class of secondary transporter is an emerging theme.
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spelling doaj-art-7db72f4e03004aed918c7ef9b701e9f02025-08-20T04:02:56ZengNature PortfolioCommunications Biology2399-36422025-08-018111110.1038/s42003-025-08591-xA new class of binding-protein dependent solute transporter exemplified by the TAXI-GltS system from Bordetella pertussisLily M. Jaques0Joseph F. S. Davies1Jack J. Sheldon-Towler2David J. Kelly3Vanessa Leone4Christopher Mulligan5School of Biosciences, Division of Natural Sciences, University of KentSchool of Biosciences, Division of Natural Sciences, University of KentSchool of Biosciences, Division of Natural Sciences, University of KentSchool of Biosciences, The University of SheffieldDepartment of Biophysics and Data Science Institute, Medical College of WisconsinSchool of Biosciences, Division of Natural Sciences, University of KentAbstract Tripartite ATP-independent periplasmic (TRAP) transporters are widespread in prokaryotes, but absent in eukaryotes, and transport various substrates. TRAP transporters are typically composed of a monomeric substrate binding protein (SBP) and a characteristic transmembrane component. Here, we describe the discovery and characterisation of a TRAP SBP from the TAXI subfamily with a previously unidentified architecture. BP0403 from Bordetella pertussis is a predicted lipoprotein with 3 distinct domains; an α/β globular domain, a helical domain and a C-terminal TAXI SBP domain. Characterisation of full-length BP0403 reveals that it forms a stable dimer, and structural modelling coupled with molecular weight analysis reveals that the interdomain helical region is solely responsible for dimerisation. Differential scanning fluorimetry (DSF) and intrinsic tyrosine fluorescence reveal that BP0403 binds L-glutamate with nanomolar affinity. Unexpectedly, genome context analysis of BP0403 reveals no TRAP membrane component genes; instead, we find co-localisation and translational coupling with gltS, encoding a Na+/glutamate symporter. In other bacteria, we identified fused BP0403-GltS homologues, strongly suggesting that this constitutes a completely novel SBP-dependent secondary active transporter. Structural comparisons suggest GltS operates by an elevator-type mechanism, like TRAP transporters; the association of an SBP with this class of secondary transporter is an emerging theme.https://doi.org/10.1038/s42003-025-08591-x
spellingShingle Lily M. Jaques
Joseph F. S. Davies
Jack J. Sheldon-Towler
David J. Kelly
Vanessa Leone
Christopher Mulligan
A new class of binding-protein dependent solute transporter exemplified by the TAXI-GltS system from Bordetella pertussis
Communications Biology
title A new class of binding-protein dependent solute transporter exemplified by the TAXI-GltS system from Bordetella pertussis
title_full A new class of binding-protein dependent solute transporter exemplified by the TAXI-GltS system from Bordetella pertussis
title_fullStr A new class of binding-protein dependent solute transporter exemplified by the TAXI-GltS system from Bordetella pertussis
title_full_unstemmed A new class of binding-protein dependent solute transporter exemplified by the TAXI-GltS system from Bordetella pertussis
title_short A new class of binding-protein dependent solute transporter exemplified by the TAXI-GltS system from Bordetella pertussis
title_sort new class of binding protein dependent solute transporter exemplified by the taxi glts system from bordetella pertussis
url https://doi.org/10.1038/s42003-025-08591-x
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