Structural Basis for Inhibition of Human Anion Transporter SLC26A6/PAT-1

Abstract

PAT-1, encoded by the gene SLC26A6, is an exchanger of small organic and inorganic anions including oxalate and chloride in the kidney and the intestines. PAT-1 dysfunction is implicated in nephrolithiasis and hyperoxaluria, and its modulation is a potential therapeutic strategy to treat cystic fibrosis. PAT-1 has two small molecule inhibitors: DIDS, a non-specific anion exchanger inhibitor; and PAT1inh-B01 which is highly specific to PAT-1. In this study, we report high-resolution cryo-electron microscopy structures of the human PAT-1 homodimer in complex with these inhibitors to reveal their different inhibition mechanisms. These structures also uncover the complex interactions between the transmembrane, STAS and N-terminal domains, with implications on its ion exchange function. Hence, this study provides mechanistic insight into PAT-1 molecular function and inhibition, and contributes to our understanding of SLC26 transport mechanisms.

Structural basis for aphidicolin inhibition of human processive DNA synthesis
A. U. Danazumi, M. Tehseen, L. Zhao +4
bioRxiv19 Oct 2026PreprintCC BY-NC-NDFull textBiophysicsbioRxiv
Structure Basis for Chloride Recognition and Transport by Human Kidney Brain Anion Transporter (KBAT)
Yurou Wang, Tengyu Xie, Songyue Wu +5
Biomolecules23 Sep 2026Peer-reviewedCC BYFull textGeneral biochemistryEurope PMC
Structural basis for phosphorylation-induced inactivation of the rice ammonium transporter AMT1;1
F. Yu, X. Huang, S. Wang +4
bioRxiv12 Oct 2026PreprintCC BYFull textBiophysicsbioRxiv
Structural basis for loop-dependent inhibition by AcrIIC1 anti-CRISPR proteins
Shen Wang, Zhiyu Zhang, Chenyu Luan +8
Nature Communications16 Oct 2026Peer-reviewedCC BY-NC-ND 4.0Full textMolecular biology & gene regulationCrossref
Mechanistical and structural basis of Kv channel inhibition by 4 aminopyridine
B. I. Pinto-Anwandter, R. Agrawal, T. Thomas +3
bioRxiv12 Sep 2026PreprintCC BYFull textBiophysicsbioRxiv

Cite

BibTeX RIS

BibTeX

@misc{chi2026structural,
  title = {{Structural Basis for Inhibition of Human Anion Transporter SLC26A6/PAT-1}},
  author = {G. Chi and T. Bohstedt and R. Adamson and A. C. W. Pike and L. Shrestha and O. Cil and M. O. Anderson and M. Izadiar and E. Williams and N. A. Burgess-Brown and J. M. Elkins and K. L. Duerr and D. B. Sauer},
  howpublished = {bioRxiv},
  year = {2026},
  month = nov,
  doi = {10.64898/2026.11.01.757131},
  url = {https://www.biorxiv.org/content/10.64898/2026.11.01.757131v1},
  note = {CC BY-NC},
}

RIS

TY  - UNPB
TI  - Structural Basis for Inhibition of Human Anion Transporter SLC26A6/PAT-1
AU  - G. Chi
AU  - T. Bohstedt
AU  - R. Adamson
AU  - A. C. W. Pike
AU  - L. Shrestha
AU  - O. Cil
AU  - M. O. Anderson
AU  - M. Izadiar
AU  - E. Williams
AU  - N. A. Burgess-Brown
AU  - J. M. Elkins
AU  - K. L. Duerr
AU  - D. B. Sauer
PY  - 2026
DA  - 2026/11/01
PB  - bioRxiv
DO  - 10.64898/2026.11.01.757131
UR  - https://www.biorxiv.org/content/10.64898/2026.11.01.757131v1
AB  - PAT-1, encoded by the gene SLC26A6, is an exchanger of small organic and inorganic anions including oxalate and chloride in the kidney and the intestines. PAT-1 dysfunction is implicated in nephrolithiasis and hyperoxaluria, and its modulation is a potential therapeutic strategy to treat cystic fibrosis. PAT-1 has two small molecule inhibitors: DIDS, a non-specific anion exchanger inhibitor; and PAT1inh-B01 which is highly specific to PAT-1. In this study, we report high-resolution cryo-electron microscopy structures of the human PAT-1 homodimer in complex with these inhibitors to reveal their different inhibition mechanisms. These structures also uncover the complex interactions between the transmembrane, STAS and N-terminal domains, with implications on its ion exchange function. Hence, this study provides mechanistic insight into PAT-1 molecular function and inhibition, and contributes to our understanding of SLC26 transport mechanisms.
ER  -

Abstract

Related

Cite