Structure and transport mechanism of human riboflavin transporters
Abstract Riboflavin (vitamin B2) is the precursor of flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), which act as key cofactors of many enzymes, thus has essential roles in cell growth and functions. Animals cannot synthesize riboflavin in situ, the intake, distribution and metabo...
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Nature Portfolio
2025-05-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-59255-7 |
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| author | Ke Wang Huiwen Chen Lili Cheng Jun Zhao Bo Huang Di Wu Xin He Yumeng Zhou Yaxuan Yuan Feng Zhou Juquan Jiang Ligong Chen Daohua Jiang |
| author_facet | Ke Wang Huiwen Chen Lili Cheng Jun Zhao Bo Huang Di Wu Xin He Yumeng Zhou Yaxuan Yuan Feng Zhou Juquan Jiang Ligong Chen Daohua Jiang |
| author_sort | Ke Wang |
| collection | DOAJ |
| description | Abstract Riboflavin (vitamin B2) is the precursor of flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), which act as key cofactors of many enzymes, thus has essential roles in cell growth and functions. Animals cannot synthesize riboflavin in situ, the intake, distribution and metabolism of which are mediated by three riboflavin transporters (RFVT1-3). Many mutations in RFVTs cause severe consequences. How RFVTs recognize and transport riboflavin remains largely unknown. Here we describe the cryo-electron microscopy structures of human RFVT2 and RFVT3 in complex with riboflavin in outward-occluded and inward-open states, respectively. Riboflavin is recognized by a conserved binding pocket in the central cavity of RFVTs, whereas two acidic residues in RFVT3 determine its pH-dependent activity. By combining the structural, computational and functional analyses, this study demonstrates the structural basis of riboflavin recognition and provides a structural framework for the mechanistic comprehension of riboflavin recognition, transport, and pathology in human RFVTs. |
| format | Article |
| id | doaj-art-9efc2eb2c87e4742a30cb0ab0b997b2e |
| institution | DOAJ |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-9efc2eb2c87e4742a30cb0ab0b997b2e2025-08-20T02:55:29ZengNature PortfolioNature Communications2041-17232025-05-0116111510.1038/s41467-025-59255-7Structure and transport mechanism of human riboflavin transportersKe Wang0Huiwen Chen1Lili Cheng2Jun Zhao3Bo Huang4Di Wu5Xin He6Yumeng Zhou7Yaxuan Yuan8Feng Zhou9Juquan Jiang10Ligong Chen11Daohua Jiang12Department of Microbiology and Biotechnology, College of Life Sciences, Northeast Agricultural UniversityDepartment of Microbiology and Biotechnology, College of Life Sciences, Northeast Agricultural UniversitySchool of Pharmaceutical Sciences, Beijing Frontier Research Center for Biological Structure, Tsinghua UniversityPeking University Institute of Advanced Agricultural Sciences, Shandong Laboratory of Advanced Agricultural Sciences at WeifangBeijing StoneWise Technology Co Ltd.Beijing National Laboratory for Condensed Matter Physics and Institute of Physics, Chinese Academy of SciencesSchool of Pharmaceutical Sciences, Beijing Frontier Research Center for Biological Structure, Tsinghua UniversitySchool of Pharmaceutical Sciences, Beijing Frontier Research Center for Biological Structure, Tsinghua UniversitySchool of Pharmaceutical Sciences, Beijing Frontier Research Center for Biological Structure, Tsinghua UniversityBeijing StoneWise Technology Co Ltd.Department of Microbiology and Biotechnology, College of Life Sciences, Northeast Agricultural UniversitySchool of Pharmaceutical Sciences, Beijing Frontier Research Center for Biological Structure, Tsinghua UniversityBeijing National Laboratory for Condensed Matter Physics and Institute of Physics, Chinese Academy of SciencesAbstract Riboflavin (vitamin B2) is the precursor of flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), which act as key cofactors of many enzymes, thus has essential roles in cell growth and functions. Animals cannot synthesize riboflavin in situ, the intake, distribution and metabolism of which are mediated by three riboflavin transporters (RFVT1-3). Many mutations in RFVTs cause severe consequences. How RFVTs recognize and transport riboflavin remains largely unknown. Here we describe the cryo-electron microscopy structures of human RFVT2 and RFVT3 in complex with riboflavin in outward-occluded and inward-open states, respectively. Riboflavin is recognized by a conserved binding pocket in the central cavity of RFVTs, whereas two acidic residues in RFVT3 determine its pH-dependent activity. By combining the structural, computational and functional analyses, this study demonstrates the structural basis of riboflavin recognition and provides a structural framework for the mechanistic comprehension of riboflavin recognition, transport, and pathology in human RFVTs.https://doi.org/10.1038/s41467-025-59255-7 |
| spellingShingle | Ke Wang Huiwen Chen Lili Cheng Jun Zhao Bo Huang Di Wu Xin He Yumeng Zhou Yaxuan Yuan Feng Zhou Juquan Jiang Ligong Chen Daohua Jiang Structure and transport mechanism of human riboflavin transporters Nature Communications |
| title | Structure and transport mechanism of human riboflavin transporters |
| title_full | Structure and transport mechanism of human riboflavin transporters |
| title_fullStr | Structure and transport mechanism of human riboflavin transporters |
| title_full_unstemmed | Structure and transport mechanism of human riboflavin transporters |
| title_short | Structure and transport mechanism of human riboflavin transporters |
| title_sort | structure and transport mechanism of human riboflavin transporters |
| url | https://doi.org/10.1038/s41467-025-59255-7 |
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