Structural basis for the reaction cycle and transport mechanism of human Na <sup>+</sup> -sulfate cotransporter NaS1 (SLC13A1)
Sulfate (SO<sub>4</sub><sup>2-</sup>) is a pivotal inorganic anion with essential roles in mammalian physiology. NaS1, a member of solute carrier 13 family and divalent anion/sodium symporter family, functions as a Na<sup>+</sup>-sulfate cotransporter, facilitating sulfate (re)absorption across renal proximal tubule and small intestine epithelia. While previous studies have linked several human disorders to mutations in the <i>NaS1</i> gene, its transport mechanism remains unclear. Here, we report the cryo-electron microscopy structures of five distinct conformations of the human NaS1 at resolutions of 2.7 to 3.3 angstroms, revealing the substrates recognition mechanism and the conformational change of NaS1 during the Na<sup>+</sup>-sulfate cotransport cycle. Our studies delineate the molecular basis of the detailed dynamic transport cycle of NaS1. These findings advance the current understanding of the Na<sup>+</sup>-sulfate cotransport mechanism, human sulfate (re)absorption, and the implications of disease-associated NaS1 mutations.
Authors
- Meiying Chen
- Sensen Zhang (ORCID: https://orcid.org/0000-0001-8827-3959)
- Yixue Wang (ORCID: https://orcid.org/0000-0001-5254-5940)
- Maojun Yang (ORCID: https://orcid.org/0000-0002-6798-3094)
- Guangyan Cai (ORCID: https://orcid.org/0000-0001-8586-6353)
- Chang Liu (ORCID: https://orcid.org/0009-0008-8169-4572)
- Xin D. Gao (ORCID: https://orcid.org/0000-0002-7108-3574)
- Boda Zhou (ORCID: https://orcid.org/0000-0001-8207-7367)
- Rui Zhang
- Jian Yin (ORCID: https://orcid.org/0000-0002-2251-8674)
- Xiangmei Chen (ORCID: https://orcid.org/0000-0001-8774-6021)
- Min Xie (ORCID: https://orcid.org/0000-0001-5659-7211)
- Xinyi Yuan (ORCID: https://orcid.org/0009-0007-3574-8018)
- Xudong Chen (ORCID: https://orcid.org/0000-0002-2989-5608)
- De Li
- Youqi Zhang
Institutions
- Hangzhou Normal University (CN)
- Chinese PLA General Hospital (CN)
- Southern University of Science and Technology (CN)
- Beijing Tsinghua Chang Gung Hospital (CN)
- Center for Life Sciences (CN)
- Beijing Academy of Science and Technology (CN)
- State Key Laboratory of Kidney Diseases
- King Abdullah University of Science and Technology (SA)
- Tsinghua University (CN)
Publication Details
- Journal
- Science Advances
- Published
- 2024-11-22
- DOI
- https://doi.org/10.1126/sciadv.ado6778
- Citations
- 2
- Primary Topic
- Ion Transport and Channel Regulation
- Type
- article
- Field-Weighted Citation Impact
- 0.47
Funders
- National Natural Science Foundation of China
- King Abdullah University of Science and Technology
- Tsinghua University