ArticleScience advances2022
The two-domain elevator-type mechanism of zinc-transporting ZIP proteins.
Article in Science advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 56 citations in OpenAlex.
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- Zinc homeostasis imbalance: Potential therapeutic value in neurodegenerative diseases.Neural regeneration research · 2026Article
- Effluxosomes and the evolution of metal resistance inInfection and immunity · 2026Review
- Zinc-induced exposure of an LxL motif drives clathrin-mediated endocytosis of the zinc transceptor ZIP4.The Journal of biological chemistry · 2026Article
- African-enriched SLC39A10 (ZIP10) missense variants differentially affect cellular zinc homeostasis and associate with health-related traits.Genes & nutrition · 2026Article
- ZFT is the major iron and zinc transporter ineLife · 2026Article
- A homology-based 3D model and structure-function studies reveal key elements for divalent metal ion transporter ZIP8 (SLC39A8) function.The Journal of biological chemistry · 2025Article
- Probing of substrate binding-induced conformational switch of a ZIP metal transporter using sandwich ELISA.Scientific reports · 2025Article
- Allosteric modulation of the solute carrier transporter SLC39A8 potentiates manganese and cadmium uptake.The Journal of clinical investigation · 2025Article
- Systematic analysis of naturally occurring missense mutations in human manganese transporters: prediction and structural insights.bioRxiv : the preprint server for biology · 2025Article
- SENP1 Senses Oxidative Stress to Regulate the SUMOylation Modification of ZIP8 and Maintain Zinc Transport Functions.Antioxidants (Basel, Switzerland) · 2025Article
- Data- and knowledge-derived functional landscape of human solute carriers.Molecular systems biology · 2025Article
- Ion-Induced Dipole Interactions Matter in Metadynamics Simulation of Transition Metal Ion Transporters.Journal of chemical theory and computation · 2025Article
- Rice Responses to Abiotic Stress: Key Proteins and Molecular Mechanisms.International journal of molecular sciences · 2025Review
- Molecular insights into substrate translocation in an elevator-type metal transporter.Nature communications · 2024Article
- Evolution, classification, and mechanisms of transport, activity regulation, and substrate specificity of ZIP metal transporters.Critical reviews in biochemistry and molecular biology · 2024Review
- Molecular insights into substrate translocation in an elevator-type metal transporter.bioRxiv : the preprint server for biology · 2024Article
- Determination of metal ion transport rate of human ZIP4 using stable zinc isotopes.The Journal of biological chemistry · 2024Article
- The Manganese-Bone Connection: Investigating the Role of Manganese in Bone Health.Journal of clinical medicine · 2024Review
- Identification and characterization of zinc importers inJournal of bacteriology · 2024Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Zinc is essential for all organisms and yet detrimental at elevated levels. Hence, homeostasis of this metal is tightly regulated. The Zrt/Irt-like proteins (ZIPs) represent the only zinc importers in metazoans. Mutations in human ZIPs cause serious disorders, but the mechanism by which ZIPs transfer zinc remains elusive. Hitherto, structural information is only available for a model member, BbZIP, and as a single, ion-bound conformation, precluding mechanistic insights. Here, we elucidate an inward-open metal-free BbZIP structure, differing substantially in the relative positions of the two separate domains of ZIPs. With accompanying coevolutional analyses, mutagenesis, and uptake assays, the data point to an elevator-type transport mechanism, likely shared within the ZIP family, unifying earlier functional data. Moreover, the structure reveals a previously unknown ninth transmembrane segment that is important for activity in vivo. Our findings outline the mechanistic principles governing ZIP-protein transport and enhance the molecular understanding of ZIP-related disorders.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.