ArticleMetallomics : integrated biometal science2015
The large intracellular loop of hZIP4 is an intrinsically disordered zinc binding domain.
Article in Metallomics : integrated biometal science, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 30 citations in OpenAlex.
- Zinc-induced exposure of an LxL motif drives clathrin-mediated endocytosis of the zinc transceptor ZIP4.The Journal of biological chemistry · 2026Article
- The structure of complexes between zinc(ii) cations and histidine-rich repeats from the unstructured N-terminal domain of human prion protein.RSC advances · 2025Review
- Metal-sensing properties of the disordered loop from the Arabidopsis metal transceptor IRT1.The Biochemical journal · 2025Article
- Evolution, classification, and mechanisms of transport, activity regulation, and substrate specificity of ZIP metal transporters.Critical reviews in biochemistry and molecular biology · 2024Review
- Unlocking the brain's zinc code: implications for cognitive function and disease.Frontiers in biophysics · 2024Article
- Research progress on the molecular structure, function, and application in tumor therapy of zinc transporter ZIP4.International journal of biological sciences · 2024Review
- The Molecular Basis for Zinc Bioavailability.International journal of molecular sciences · 2023Review
- Heterologous Expression of Full-Length and Truncated Human ZIP4 Zinc Transporter inBiomolecules · 2022Article
- Genome-Wide Identification and Expression Profile Reveal Potential Roles of PeanutPlants (Basel, Switzerland) · 2022Article
- The Effects of Tetrapeptides Designed to Fit the Androgen Binding Site of ZIP9 on Myogenic and Osteogenic Cells.Biology · 2021Article
- The Function and Regulation of Zinc in the Brain.Neuroscience · 2021Review
- Zap70 Regulates TCR-Mediated Zip6 Activation at the Immunological Synapse.Frontiers in immunology · 2021Article
- Why and how to investigate the role of protein phosphorylation in ZIP and ZnT zinc transporter activity and regulation.Cellular and molecular life sciences : CMLS · 2020Review
- Molecular Basis of Zinc-Dependent Endocytosis of Human ZIP4 Transceptor.Cell reports · 2020Article
- The histidine-rich loop in the extracellular domain of ZIP4 binds zinc and plays a role in zinc transport.The Biochemical journal · 2019Article
- Concomitant disorder and high-affinity zinc binding in the human zinc- and iron-regulated transport protein 4 intracellular loop.Protein science : a publication of the Protein Society · 2019Article
- Computation and Functional Studies Provide a Model for the Structure of the Zinc Transporter hZIP4.The Journal of biological chemistry · 2015Article
- Zinc transporters and their functional integration in mammalian cells.The Journal of biological chemistryReview
- The emerging role of zinc transporters in cellular homeostasis and cancer.Signal transduction and targeted therapyArticle
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The human (h) ZIP4 transporter is a plasma membrane protein which functions to increase the cytosolic concentration of zinc. hZIP4 transports zinc into intestinal cells and therefore has a central role in the absorption of dietary zinc. hZIP4 has eight transmembrane domains and encodes a large intracellular loop between transmembrane domains III and IV, M3M4. Previously, it has been postulated that this domain regulates hZIP4 levels in the plasma membrane in a zinc-dependent manner. The objective of this research was to examine the zinc binding properties of the large intracellular loop of hZIP4. Therefore, we have recombinantly expressed and purified M3M4 and showed that this domain binds two zinc ions. Using a combination of site-directed mutagenesis, metal binding affinity assays, and X-ray absorption spectroscopy, we demonstrated that the two Zn(2+) ions bind sequentially, with the first Zn(2+) binding to a CysHis3 site with a nanomolar binding affinity, and the second Zn(2+) binding to a His4 site with a weaker affinity. Circular dichroism spectroscopy revealed that the M3M4 domain is intrinsically disordered, with only a small structural change induced upon Zn(2+) coordination. Our data supports a model in which the intracellular M3M4 domain senses high cytosolic Zn(2+) concentrations and regulates the plasma membrane levels of the hZIP4 transporter in response to Zn(2+) binding.
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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.