Structural basis for the reaction cycle and transport mechanism of human Na + -sulfate cotransporter NaS1 (SLC13A1)
Year: 2024
Type: article
Abstract: Sulfate (SO 4 2− ) 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 + -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 NaS1 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 + -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 + -sulfate cotransport mechanism, human sulfate (re)absorption, and the implications of disease-associated NaS1 mutations.
Source: Science Advances
Authors: Xudong Chen, Xudong Chen, Youqi Zhang, Jian Yin, Chang Liu, Min Xie, Yixue Wang, Meiying Chen, Rui Zhang, Xinyi Yuan, De Li, Xiangmei Chen, Xiangmei Chen, Xin Gao, Guangyan Cai, Sensen Zhang, Boda Zhou, Maojun Yang
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,500
OpenAlex ID: W4404627593