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TitleSLC26A11 is an atypical solute carrier with dual transport-channel function mediating lysosomal sulfate transport.
Journal, issue, pagesNat Commun, Vol. 17, Issue 1, Year 2026
Publish dateJul 27, 2026
AuthorsBenedikt T Kuhn / Peter Kovermann / Bassam G Haddad / Tim Rasmussen / Tamsanqa T Hove / Stefanie Bungert-Plümke / Bettina Böttcher / Jan-Philipp Machtens / Christoph Fahlke / Eric R Geertsma /
PubMed AbstractMembrane 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 ...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.
External linksNat Commun / PubMed:42509233 / PubMed Central
MethodsEM (single particle)
Resolution2.8 - 3.2 Å
Structure data

52784

9iar

EMDB-52784, PDB-9iar:
Sulfate transporter SLC26A11 in nanodiscs with nanobody Nb11
Method: EM (single particle) / Resolution: 3.2 Å

52785

9ias

EMDB-52785, PDB-9ias:
Sulfate transporter SLC26A11 in nanodiscs with nanobody Nb4
Method: EM (single particle) / Resolution: 2.8 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

ChemComp-CL:
Unknown entry

ChemComp-PEE:
1,2-dioleoyl-sn-glycero-3-phosphoethanolamine / DOPE, phospholipid*YM

ChemComp-HOH:
WATER

Source
  • homo sapiens (human)
  • vicugna pacos (alpaca)
KeywordsMEMBRANE PROTEIN / sulfate transporter / chloride channel / lysosome

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