ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2020
Asymmetric functions of a binuclear metal center within the transport pathway of a human zinc transporter ZIP4.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 53 citations in OpenAlex.
- African-enriched SLC39A10 (ZIP10) missense variants differentially affect cellular zinc homeostasis and associate with health-related traits.Genes & nutrition · 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
- Ion-Induced Dipole Interactions Matter in Metadynamics Simulation of Transition Metal Ion Transporters.Journal of chemical theory and computation · 2025Article
- 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
- Structures, Mechanisms, and Physiological Functions of Zinc Transporters in Different Biological Kingdoms.International journal of molecular sciences · 2024Review
- Research progress on the molecular structure, function, and application in tumor therapy of zinc transporter ZIP4.International journal of biological sciences · 2024Review
- Metalation and activation of ZnBiophysics reviews · 2023Review
- Rational engineering of an elevator-type metal transporter ZIP8 reveals a conditional selectivity filter critically involved in determining substrate specificity.Communications biology · 2023Article
- Structural mechanism of intracellular autoregulation of zinc uptake in ZIP transporters.Nature communications · 2023Article
- The Molecular Basis for Zinc Bioavailability.International journal of molecular sciences · 2023Review
- Functional characterization of SLC39 family members ZIP5 and ZIP10 in overexpressing HEK293 cells reveals selective copper transport activity.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2023Article
- Structural insights into the elevator-type transport mechanism of a bacterial ZIP metal transporter.Nature communications · 2023Article
- Zinc/iron-regulated transporter-like protein gene family inFrontiers in plant science · 2023Article
- Expression, purification, crystallization of a ZIP metal transporter from Bordetella bronchiseptica (BbZIP).Methods in enzymology · 2023Article
- The two-domain elevator-type mechanism of zinc-transporting ZIP proteins.Science advances · 2022Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Metal clusters are exploited by numerous metalloenzymes for catalysis, but it is not common to utilize a metal cluster for substrate transport across membrane. The recent crystal structure of a prototypic Zrt-/Irt-like protein (ZIP) metal transporter from Bordetella bronchiseptica (BbZIP) revealed an unprecedented binuclear metal center (BMC) within the transport pathway. Here, through a combination of bioinformatics, biochemical and structural approaches, we concluded that the two physically associated metal-binding sites in the BMC of human ZIP4 (hZIP4) zinc transporter exert different functions: one conserved transition metal-binding site acts as the transport site essential for activity, whereas the variable metal-binding site is required for hZIP4's optimal activity presumably by serving as a secondary transport site and modulating the properties of the primary transport site. Sequential soaking experiments on BbZIP crystals clarified the process of metal release from the BMC to the bulky solvent. This work provides important insights into the transport mechanism of the ZIPs broadly involved in transition metal homeostasis and signaling, and also a paradigm on a novel function of metal cluster in metalloproteins.
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Registered trials
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