Structural mechanism of intracellular autoregulation of zinc uptake in ZIP transporters
Abstract Zinc is an essential micronutrient that supports all living organisms through regulating numerous biological processes. However, the mechanism of uptake regulation by intracellular Zn2+ status remains unclear. Here we report a cryo-electron microscopy structure of a ZIP-family transporter f...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-06-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-39010-6 |
| _version_ | 1797806584172118016 |
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| author | Changxu Pang Jin Chai Ping Zhu John Shanklin Qun Liu |
| author_facet | Changxu Pang Jin Chai Ping Zhu John Shanklin Qun Liu |
| author_sort | Changxu Pang |
| collection | DOAJ |
| description | Abstract Zinc is an essential micronutrient that supports all living organisms through regulating numerous biological processes. However, the mechanism of uptake regulation by intracellular Zn2+ status remains unclear. Here we report a cryo-electron microscopy structure of a ZIP-family transporter from Bordetella bronchiseptica at 3.05 Å resolution in an inward-facing, inhibited conformation. The transporter forms a homodimer, each protomer containing nine transmembrane helices and three metal ions. Two metal ions form a binuclear pore structure, and the third ion is located at an egress site facing the cytoplasm. The egress site is covered by a loop, and two histidine residues on the loop interact with the egress-site ion and regulate its release. Cell-based Zn2+ uptake and cell growth viability assays reveal a negative regulation of Zn2+ uptake through sensing intracellular Zn2+ status using a built-in sensor. These structural and biochemical analyses provide mechanistic insight into the autoregulation of zinc uptake across membranes. |
| first_indexed | 2024-03-13T06:09:28Z |
| format | Article |
| id | doaj.art-85ee236294074551ab3e0ac75f34941e |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-13T06:09:28Z |
| publishDate | 2023-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-85ee236294074551ab3e0ac75f34941e2023-06-11T11:19:48ZengNature PortfolioNature Communications2041-17232023-06-0114111010.1038/s41467-023-39010-6Structural mechanism of intracellular autoregulation of zinc uptake in ZIP transportersChangxu Pang0Jin Chai1Ping Zhu2John Shanklin3Qun Liu4Biology Department, Brookhaven National LaboratoryBiology Department, Brookhaven National LaboratoryBiology Department, Brookhaven National LaboratoryBiology Department, Brookhaven National LaboratoryBiology Department, Brookhaven National LaboratoryAbstract Zinc is an essential micronutrient that supports all living organisms through regulating numerous biological processes. However, the mechanism of uptake regulation by intracellular Zn2+ status remains unclear. Here we report a cryo-electron microscopy structure of a ZIP-family transporter from Bordetella bronchiseptica at 3.05 Å resolution in an inward-facing, inhibited conformation. The transporter forms a homodimer, each protomer containing nine transmembrane helices and three metal ions. Two metal ions form a binuclear pore structure, and the third ion is located at an egress site facing the cytoplasm. The egress site is covered by a loop, and two histidine residues on the loop interact with the egress-site ion and regulate its release. Cell-based Zn2+ uptake and cell growth viability assays reveal a negative regulation of Zn2+ uptake through sensing intracellular Zn2+ status using a built-in sensor. These structural and biochemical analyses provide mechanistic insight into the autoregulation of zinc uptake across membranes.https://doi.org/10.1038/s41467-023-39010-6 |
| spellingShingle | Changxu Pang Jin Chai Ping Zhu John Shanklin Qun Liu Structural mechanism of intracellular autoregulation of zinc uptake in ZIP transporters Nature Communications |
| title | Structural mechanism of intracellular autoregulation of zinc uptake in ZIP transporters |
| title_full | Structural mechanism of intracellular autoregulation of zinc uptake in ZIP transporters |
| title_fullStr | Structural mechanism of intracellular autoregulation of zinc uptake in ZIP transporters |
| title_full_unstemmed | Structural mechanism of intracellular autoregulation of zinc uptake in ZIP transporters |
| title_short | Structural mechanism of intracellular autoregulation of zinc uptake in ZIP transporters |
| title_sort | structural mechanism of intracellular autoregulation of zinc uptake in zip transporters |
| url | https://doi.org/10.1038/s41467-023-39010-6 |
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