Cryo-EM structures of human zinc transporter ZnT7 reveal the mechanism of Zn2+ uptake into the Golgi apparatus
Abstract Zinc ions (Zn2+) are vital to most cells, with the intracellular concentrations of Zn2+ being tightly regulated by multiple zinc transporters located at the plasma and organelle membranes. We herein present the 2.2-3.1 Å-resolution cryo-EM structures of a Golgi-localized human Zn2+/H+ antip...
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| Format: | Article |
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Nature Portfolio
2023-08-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-40521-5 |
| _version_ | 1797558396201730048 |
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| author | Han Ba Bui Satoshi Watanabe Norimichi Nomura Kehong Liu Tomoko Uemura Michio Inoue Akihisa Tsutsumi Hiroyuki Fujita Kengo Kinoshita Yukinari Kato So Iwata Masahide Kikkawa Kenji Inaba |
| author_facet | Han Ba Bui Satoshi Watanabe Norimichi Nomura Kehong Liu Tomoko Uemura Michio Inoue Akihisa Tsutsumi Hiroyuki Fujita Kengo Kinoshita Yukinari Kato So Iwata Masahide Kikkawa Kenji Inaba |
| author_sort | Han Ba Bui |
| collection | DOAJ |
| description | Abstract Zinc ions (Zn2+) are vital to most cells, with the intracellular concentrations of Zn2+ being tightly regulated by multiple zinc transporters located at the plasma and organelle membranes. We herein present the 2.2-3.1 Å-resolution cryo-EM structures of a Golgi-localized human Zn2+/H+ antiporter ZnT7 (hZnT7) in Zn2+-bound and unbound forms. Cryo-EM analyses show that hZnT7 exists as a dimer via tight interactions in both the cytosolic and transmembrane (TM) domains of two protomers, each of which contains a single Zn2+-binding site in its TM domain. hZnT7 undergoes a TM-helix rearrangement to create a negatively charged cytosolic cavity for Zn2+ entry in the inward-facing conformation and widens the luminal cavity for Zn2+ release in the outward-facing conformation. An exceptionally long cytosolic histidine-rich loop characteristic of hZnT7 binds two Zn2+ ions, seemingly facilitating Zn2+ recruitment to the TM metal transport pathway. These structures permit mechanisms of hZnT7-mediated Zn2+ uptake into the Golgi to be proposed. |
| first_indexed | 2024-03-10T17:30:51Z |
| format | Article |
| id | doaj.art-9f73ce98b94448a691a914cd33c09204 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-10T17:30:51Z |
| publishDate | 2023-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-9f73ce98b94448a691a914cd33c092042023-11-20T10:02:49ZengNature PortfolioNature Communications2041-17232023-08-0114111610.1038/s41467-023-40521-5Cryo-EM structures of human zinc transporter ZnT7 reveal the mechanism of Zn2+ uptake into the Golgi apparatusHan Ba Bui0Satoshi Watanabe1Norimichi Nomura2Kehong Liu3Tomoko Uemura4Michio Inoue5Akihisa Tsutsumi6Hiroyuki Fujita7Kengo Kinoshita8Yukinari Kato9So Iwata10Masahide Kikkawa11Kenji Inaba12Institute of Multidisciplinary Research for Advanced Materials, Tohoku UniversityInstitute of Multidisciplinary Research for Advanced Materials, Tohoku UniversityDepartment of Cell Biology, Graduate School of Medicine, Kyoto UniversityDepartment of Cell Biology, Graduate School of Medicine, Kyoto UniversityDepartment of Cell Biology, Graduate School of Medicine, Kyoto UniversityInstitute of Multidisciplinary Research for Advanced Materials, Tohoku UniversityGraduate School of Medicine, The University of TokyoAdvanced Research Laboratory, Canon Medical Systems CorporationDepartment of System Bioinformatics, Graduate School of Information Sciences, Tohoku UniversityGraduate School of Medicine, Tohoku UniversityDepartment of Cell Biology, Graduate School of Medicine, Kyoto UniversityGraduate School of Medicine, The University of TokyoInstitute of Multidisciplinary Research for Advanced Materials, Tohoku UniversityAbstract Zinc ions (Zn2+) are vital to most cells, with the intracellular concentrations of Zn2+ being tightly regulated by multiple zinc transporters located at the plasma and organelle membranes. We herein present the 2.2-3.1 Å-resolution cryo-EM structures of a Golgi-localized human Zn2+/H+ antiporter ZnT7 (hZnT7) in Zn2+-bound and unbound forms. Cryo-EM analyses show that hZnT7 exists as a dimer via tight interactions in both the cytosolic and transmembrane (TM) domains of two protomers, each of which contains a single Zn2+-binding site in its TM domain. hZnT7 undergoes a TM-helix rearrangement to create a negatively charged cytosolic cavity for Zn2+ entry in the inward-facing conformation and widens the luminal cavity for Zn2+ release in the outward-facing conformation. An exceptionally long cytosolic histidine-rich loop characteristic of hZnT7 binds two Zn2+ ions, seemingly facilitating Zn2+ recruitment to the TM metal transport pathway. These structures permit mechanisms of hZnT7-mediated Zn2+ uptake into the Golgi to be proposed.https://doi.org/10.1038/s41467-023-40521-5 |
| spellingShingle | Han Ba Bui Satoshi Watanabe Norimichi Nomura Kehong Liu Tomoko Uemura Michio Inoue Akihisa Tsutsumi Hiroyuki Fujita Kengo Kinoshita Yukinari Kato So Iwata Masahide Kikkawa Kenji Inaba Cryo-EM structures of human zinc transporter ZnT7 reveal the mechanism of Zn2+ uptake into the Golgi apparatus Nature Communications |
| title | Cryo-EM structures of human zinc transporter ZnT7 reveal the mechanism of Zn2+ uptake into the Golgi apparatus |
| title_full | Cryo-EM structures of human zinc transporter ZnT7 reveal the mechanism of Zn2+ uptake into the Golgi apparatus |
| title_fullStr | Cryo-EM structures of human zinc transporter ZnT7 reveal the mechanism of Zn2+ uptake into the Golgi apparatus |
| title_full_unstemmed | Cryo-EM structures of human zinc transporter ZnT7 reveal the mechanism of Zn2+ uptake into the Golgi apparatus |
| title_short | Cryo-EM structures of human zinc transporter ZnT7 reveal the mechanism of Zn2+ uptake into the Golgi apparatus |
| title_sort | cryo em structures of human zinc transporter znt7 reveal the mechanism of zn2 uptake into the golgi apparatus |
| url | https://doi.org/10.1038/s41467-023-40521-5 |
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