SLC26A11 is an atypical solute carrier with dual transport-channel function mediating lysosomal sulfate transport.

Overview

1. Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
2. Institute of Biological Information Processing, Molekular- und Zellphysiologie (IBI-1), Forschungszentrum Jülich, Jülich, Germany
3. Institute of Neurophysiology, Hannover Medical School, Hannover, Germany
4. University of Würzburg, Rudolf Virchow Centre, Würzburg, Germany
5. University of Würzburg, Biocentre, Chair of Biochemistry II, Würzburg, Germany

Abstract

Membrane transporters and channels are generally assumed to be based on distinct structural and functional principles. SLC26A11, a solute carrier with high expression levels in the brain, has been proposed to function as either an anion transporter or a channel. Here, we resolve this apparent discrepancy by demonstrating that SLC26A11 is a dual-function protein capable of operating as both a sulfate transporter and a chloride channel. By resolving its structure and combining biochemical studies and molecular dynamics simulations, we show that SLC26A11 exhibits all the hallmarks of a secondary transporter. The mechanistic basis for its selective ion transport identifies the protein as the elusive lysosomal sulfate exporter. Additionally, we demonstrate that SLC26A11 exhibits an uncoupled, channel-like chloride conductance gated by proton:sulfate symport. Our finding that the chloride-conducting state arises from the transport cycle may contribute to the development of therapeutic strategies for treating brain edema, and the identification of its role in lysosome sulfate efflux may provide new approaches to study and treat lysosomal storage diseases.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

No file of the authors' code could be read here: it is described below, and read at its source.

Code availability

The Python script used in the calculation of kinetic constants from MD simulations is available at https://jugit.fz-juelich.de/computational-neurophysiology/SLC26A11-ion-binding.

Reproduced under the paper's license (CC BY), from the paper cited above.

Tracing map

Proposed by the machine: these links were found in the paper and verified at the source, without human review. The map will receive a Zenodo DOI once one of the paper's authors has validated it with their ORCID.

What the map holds:

• 1 repository of the authors' code, each at its verified commit, with its license and how the link was found in the paper;
• 0 scripts, each with its path and the digest of its content;
• no match between paragraphs and code yet;
• neither the text of the paper nor the code itself.

Its JSON (tracing-map.json) is deposited on Zenodo with its DOI once the map is validated.

Data

Datasets cited

• alphafold.ebi.ac.uk/entry/q86wa9, at EMBL-EBI; found in “Data availability”
• ebi.ac.uk/emdb/emd-52784, at EMBL-EBI; found in “Data availability”
• ebi.ac.uk/emdb/emd-56650, at EMBL-EBI; found in “Data availability”
• ebi.ac.uk/emdb/emd-56651, at EMBL-EBI; found in “Data availability”

Data Availability Statement

Source Data are provided with this paper. The EM maps of nanodisc-reconstituted SLC26A11 in complex with Nb4 and Nb11 have been deposited in the Electron Microscopy Data Bank (EMDB) and corresponding atomic models have been deposited in the RSCB Protein Data Bank (PDB) with the accession codes EMD-52785 (https://www.ebi.ac.uk/emdb/EMD-52784), EMD-56651 (https://www.ebi.ac.uk/emdb/EMD-56651), plus 9IAS (https://doi.org/10.2210/pdb9IAS/pdb) (SLC26A11 in complex with Nb4) and EMD-52784 (https://www.ebi.ac.uk/emdb/EMD-52784), EMD-56650 (https://www.ebi.ac.uk/emdb/EMD-56650), plus 9IAR (https://doi.org/10.2210/pdb9iar/pdb) (SLC26A11 in complex with Nb11). The AlphaFold model of SLC26A11 used for Fig. 6 is AF-Q86WA9-F1-v6 (https://alphafold.ebi.ac.uk/entry/Q86WA9). All raw data are available upon request. Source data are provided with this paper.

The Python script used in the calculation of kinetic constants from MD simulations is available at https://jugit.fz-juelich.de/computational-neurophysiology/SLC26A11-ion-binding.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 10 authors, 4 keywords, 11 MeSH terms, 2 funders, 107 references.

Cite

This paper

Kuhn, B. T., Kovermann, P., Haddad, B. G., Rasmussen, T., Hove, T. T., Bungert-Plümke, S., Böttcher, B., Machtens, J.-P., Fahlke, C., & Geertsma, E. R. (2026). SLC26A11 is an atypical solute carrier with dual transport-channel function mediating lysosomal sulfate transport. Nature communications, 17(1), 7407. https://doi.org/10.1038/s41467-026-75749-4

The tracing map gets a citation of its own once an author has validated it and it has a DOI.

Similar papers

The papers with a page that share the most with this one: the tools found in their code, their categories, datasets, cited references and authors, the rarest counting most.

[1] doi:10.1186/s40478-026-02399-4

Overactive EAAT1 Cl<sup>-</sup> channels impair GABAergic tonic inhibition in SLC1A3-associated episodic ataxia.

Journal: Acta neuropathologica communications

In common: cellular / molecular, 4 references, 2 authors

[2] doi:10.1038/s41467-026-76831-7

Structural origins of species-specific differences in TRPV2 activation.

Journal: Nature communications

In common: histology / microscopy, cellular / molecular, 5 references

[3] doi:10.1038/s41467-026-71619-1

Structurally exclusive Teneurin complexes orchestrate divergent programs in early cortical development.

Journal: Nature communications

In common: histology / microscopy, 5 references

[4] doi:10.1038/s41586-026-10391-0 [code]

Cell-type-targeted mitochondrial transplantation rescues cell degeneration.

Journal: Nature

In common: cellular / molecular, 4 references

[5] doi:10.1038/s41467-026-76368-9

Integrative structural analysis of human endosomal NHE6 reveals a lipid-associated gate and disordered C-terminus.

Journal: Nature communications

In common: histology / microscopy, cellular / molecular, 4 references

[6] doi:10.1038/s41467-026-75877-x

Structure of NHE6 and its lipid-mediated interactions regulating endosomal pH.

Journal: Nature communications

In common: histology / microscopy, cellular / molecular, 4 references

[7] doi:10.1038/s41467-026-70575-0

Structure of a pH-sensitive pentameric ligand-gated ion channel from the Sarcoptes scabies mite.

Journal: Nature communications

In common: histology / microscopy, cellular / molecular, 4 references

[8] doi:10.1038/s41467-026-74814-2

Structural mechanism of Necrocide 1 activation of human TRPM4 that triggers necrosis by sodium overload.

Journal: Nature communications

In common: histology / microscopy, cellular / molecular, 4 references

[9] doi:10.1038/s41467-026-74087-9 [code]

Cryo-EM structures of heteromeric Kir4.1/5.1 channel suggest mechanisms of inward rectification and channel blockage.

Journal: Nature communications

In common: histology / microscopy, cellular / molecular, 4 references

[10] doi:10.1038/s41594-026-01845-0

Conformational plasticity of human acid-sensing ion channel 1a.

Journal: Nature structural & molecular biology

In common: histology / microscopy, cellular / molecular, 4 references

Contribute

The authors of this paper can claim it, correct its record and validate its tracing map, and the maintainers of its code (its owner, or a public member of its organization) correct what it says of their repository; anyone signed in can ask for its removal. Every request goes to OSCR's own machine, which answers it; your account page follows them.

Request its removal

To ask OSCR to remove this record, the copies of its authors' scripts or its tracing map, use the removal request page: signed in, you say who you are, what to remove and why, then review and confirm the request. Published rules decide every request (how).

Discussion: questions and error reports about this paper and its code, from signed-in readers and its authors. It opens with sign-in.

Reproductions: reports from readers who ran the authors' code: what they reproduced, with which environment, commit and data. It opens with sign-in.

Activity: what happens around this paper: new versions of its record, its map's validation, discussions and reproductions. It opens with sign-in.