Structural basis of isethionate transport by a TRAP transporter from a sulfate-reducing bacterium
Sulfate-reducing bacteria import organosulfur compounds from the environment for anaerobic respiration. They contribute to human disease and are problematic in industrial settings because they produce hydrogen sulfide. Here, we demonstrate how the sulfate-reducing bacterium Oleidesulfovibrio alaskensis imports isethionate, a common organosulfonate, using a tripartite ATP-independent periplasmic (TRAP) transporter (OaIsePQM). The cryo-EM structure of isethionate-bound OaIseQM to 2.98 Å resolution defines the substrate-binding site, two Na<sup>+</sup>-binding sites, and a distinct fusion helix. Key residues within the OaIseQM substrate-binding site are identified using substitution and proteoliposome assays. Functional studies demonstrate that OaIseQM requires the substrate-binding protein (OaIseP) and a Na<sup>+</sup> gradient to drive transport. Modeling of the OaIsePQM complex supports that elevator-type conformational changes are involved in this unique coupled transport process. This work expands our knowledge of the transport of organosulfur compounds in bacteria and establishes OaIsePQM as a new model system for exploring the mechanism of TRAP transporters.
Authors
- Mariafrancesca Scalise (ORCID: https://orcid.org/0000-0003-3860-6844)
- Michael Currie (ORCID: https://orcid.org/0000-0003-1509-7581)
- Sepideh Valimehr (ORCID: https://orcid.org/0000-0001-5845-8100)
- Rachel A. North (ORCID: https://orcid.org/0000-0001-5011-1567)
- Renwick C. J. Dobson (ORCID: https://orcid.org/0000-0002-5506-4939)
- Peter D. Mace (ORCID: https://orcid.org/0000-0003-2175-9537)
- Jane R. Allison (ORCID: https://orcid.org/0000-0002-5699-1726)
- Sam A. Jamieson (ORCID: https://orcid.org/0000-0003-0120-4737)
- Eric Hanssen (ORCID: https://orcid.org/0000-0002-4064-1844)
- Hamish G. Brown (ORCID: https://orcid.org/0000-0003-2292-7766)
- Santosh Panjikar (ORCID: https://orcid.org/0000-0001-7429-3879)
- James S. Davies (ORCID: https://orcid.org/0000-0003-4029-1650)
- Cesare Indiveri
- Michael C. Newton-Vesty
- Kelsi R. Hall (ORCID: https://orcid.org/0000-0001-5611-3010)
- Andrew E. Whitten (ORCID: https://orcid.org/0000-0001-8856-3120)
- Zachary D. Tillett
- Senwei Quan
Institutions
- The University of Sydney (AU)
- Australian Nuclear Science and Technology Organisation (AU)
- Australian Research Council (AU)
- Victor Chang Cardiac Research Institute (AU)
- Australian Synchrotron (AU)
- Maurice Wilkins Centre (NZ)
- Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies (IT)
- University of Calabria (IT)
- University of Otago (NZ)
- MacDiarmid Institute for Advanced Materials and Nanotechnology (NZ)
Publication Details
- Journal
- Structure
- Published
- 2025-11-05
- DOI
- https://doi.org/10.1016/j.str.2025.10.011
- Primary Topic
- Environmental Chemistry and Analysis
- Type
- article
- Field-Weighted Citation Impact
- 0.00