Structural mechanism of intracellular autoregulation of zinc uptake in ZIP transporters

Pang, Changxu; Chai, Jin; Zhu, Ping; Shanklin, John; Liu, Qun

doi:10.1038/s41467-023-39010-6

Title: Structural mechanism of intracellular autoregulation of zinc uptake in ZIP transporters

Journal Article · 08 June 2023 · Nature Communications

DOI: https://doi.org/10.1038/s41467-023-39010-6 · OSTI ID:1984562

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Abstract Zinc is an essential micronutrient that supports all living organisms through regulating numerous biological processes. However, the mechanism of uptake regulation by intracellular Zn ²⁺ 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 Zn ²⁺ uptake and cell growth viability assays reveal a negative regulation of Zn ²⁺ uptake through sensing intracellular Zn ²⁺ status using a built-in sensor. These structural and biochemical analyses provide mechanistic insight into the autoregulation of zinc uptake across membranes.

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Research Organization:: Brookhaven National Laboratory (BNL), Upton, NY (United States)

Sponsoring Organization:: USDOE; USDOE Office of Science (SC), Biological and Environmental Research (BER)

Grant/Contract Number:: SC0012704

OSTI ID:: 1984562

Report Number(s):: BNL--224350-2023-JAAM; 3404; PII: 39010

Journal Information:: Nature Communications, Journal Name: Nature Communications Journal Issue: 1 Vol. 14; ISSN 2041-1723

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United Kingdom

Language:: English

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59 BASIC BIOLOGICAL SCIENCES
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Title: Structural mechanism of intracellular autoregulation of zinc uptake in ZIP transporters

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