{"title":"人SLC26A7底物识别机制的结构基础","authors":"Xiaorong Li, Xiaoxu Yang, Xiaoli Lu, Bingqian Lin, Yuanyuan Zhang, Bangdong Huang, Yutong Zhou, Jing Huang, Kun Wu, Qiang Zhou, Ximin Chi","doi":"10.1038/s41467-025-62792-w","DOIUrl":null,"url":null,"abstract":"<p>Solute carrier family 26 (SLC26) mainly mediates transmembrane transport of various anion ions, including chloride and other halide ions, bicarbonate, oxalate, and sulfate. Many severe hereditary human diseases are correlated with SLC26 protein mutations. Here we report cryo-EM structures of human SLC26A7 in apo and iodide binding states. We identify non-canonical binding site for halide ions in SLC26A7. Molecular dynamics simulation and electrophysiological assay confirm the functional importance of key residues involved in iodide and chloride coordination. Together, our discovery marks a step towards an in-depth understanding of SLC26 family protein transport mechanisms.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"8 1","pages":""},"PeriodicalIF":15.7000,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Structural basis for substrate recognition mechanism of human SLC26A7\",\"authors\":\"Xiaorong Li, Xiaoxu Yang, Xiaoli Lu, Bingqian Lin, Yuanyuan Zhang, Bangdong Huang, Yutong Zhou, Jing Huang, Kun Wu, Qiang Zhou, Ximin Chi\",\"doi\":\"10.1038/s41467-025-62792-w\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Solute carrier family 26 (SLC26) mainly mediates transmembrane transport of various anion ions, including chloride and other halide ions, bicarbonate, oxalate, and sulfate. Many severe hereditary human diseases are correlated with SLC26 protein mutations. Here we report cryo-EM structures of human SLC26A7 in apo and iodide binding states. We identify non-canonical binding site for halide ions in SLC26A7. Molecular dynamics simulation and electrophysiological assay confirm the functional importance of key residues involved in iodide and chloride coordination. Together, our discovery marks a step towards an in-depth understanding of SLC26 family protein transport mechanisms.</p>\",\"PeriodicalId\":19066,\"journal\":{\"name\":\"Nature Communications\",\"volume\":\"8 1\",\"pages\":\"\"},\"PeriodicalIF\":15.7000,\"publicationDate\":\"2025-08-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Nature Communications\",\"FirstCategoryId\":\"103\",\"ListUrlMain\":\"https://doi.org/10.1038/s41467-025-62792-w\",\"RegionNum\":1,\"RegionCategory\":\"综合性期刊\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MULTIDISCIPLINARY SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature Communications","FirstCategoryId":"103","ListUrlMain":"https://doi.org/10.1038/s41467-025-62792-w","RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}
Structural basis for substrate recognition mechanism of human SLC26A7
Solute carrier family 26 (SLC26) mainly mediates transmembrane transport of various anion ions, including chloride and other halide ions, bicarbonate, oxalate, and sulfate. Many severe hereditary human diseases are correlated with SLC26 protein mutations. Here we report cryo-EM structures of human SLC26A7 in apo and iodide binding states. We identify non-canonical binding site for halide ions in SLC26A7. Molecular dynamics simulation and electrophysiological assay confirm the functional importance of key residues involved in iodide and chloride coordination. Together, our discovery marks a step towards an in-depth understanding of SLC26 family protein transport mechanisms.
期刊介绍:
Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.