ArticleBiophysical journal2022
Dynamical interplay between the human high-affinity copper transporter hCtr1 and its cognate metal ion.
Article in Biophysical journal, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- Comprehensive analysis of regulated cell death pathways: intrinsic disorder, protein-protein interactions, and cross-pathway communication.Apoptosis : an international journal on programmed cell death · 2025Pooled it
- Article
- Reduction in Hepatic Phosphatidylcholine Biosynthesis Promotes MASH Through Copper Deficiency.bioRxiv : the preprint server for biology · 2026Article
- Human CTR1 Through the Ages: Milestones and Emerging Roles in Disease and Therapy.Biomolecules · 2025Review
- Elevated intracellular copper induces CTR1 monomerization and prevents copper uptake.Nature communications · 2025Article
- Structural investigations connect the disordered N-terminal extension of HypB to the activities of HypB and SlyD in E. coli.Protein science : a publication of the Protein Society · 2025Article
- Exploring the Gating Mechanism of the Human Copper Transporter, hCtr1, Using EPR Spectroscopy.Biomolecules · 2025Article
- Mammalian copper homeostasis: physiological roles and molecular mechanisms.Physiological reviews · 2025Review
- Roles of Copper Transport Systems Members in Breast Cancer.Cancer medicine · 2024Review
- Tracking Disordered Extracellular Domains of Membrane Proteins in the Cell with Cu(II)-Based Spin Labels.The journal of physical chemistry. B · 2024Article
- Mitochondrial pathways of copper neurotoxicity: focus on mitochondrial dynamics and mitophagy.Frontiers in molecular neuroscience · 2024Review
- Intrinsically disordered ectodomain modulates ion permeation through a metal transporter.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- EPR Spectroscopy Provides New Insights into Complex Biological Reaction Mechanisms.The journal of physical chemistry. B · 2022Review
- Disrupting Cu trafficking as a potential therapy for cancer.Frontiers in molecular biosciences · 2022Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Abnormal cellular copper levels have been clearly implicated in genetic diseases, cancer, and neurodegeneration. Ctr1, a high-affinity copper transporter, is a homotrimeric integral membrane protein that provides the main route for cellular copper uptake. Together with a sophisticated copper transport system, Ctr1 regulates Cu(I) metabolism in eukaryotes. Despite its pivotal role in normal cell function, the molecular mechanism of copper uptake and transport via Ctr1 remains elusive. In this study, electron paramagnetic resonance (EPR), UV-visible spectroscopy, and all-atom simulations were employed to explore Cu(I) binding to full-length human Ctr1 (hCtr1), thereby elucidating how metal binding at multiple distinct sites affects the hCtr1 conformational dynamics. We demonstrate that each hCtr1 monomer binds up to five Cu(I) ions and that progressive Cu(I) binding triggers a marked structural rearrangement in the hCtr1 C-terminal region. The observed Cu(I)-induced conformational remodeling suggests that the C-terminal region may play a dual role, serving both as a channel gate and as a shuttle mediating the delivery of copper ions from the extracellular hCtr1 selectivity filter to intracellular metallochaperones. Our findings thus contribute to a more complete understanding of the mechanism of hCtr1-mediated Cu(I) uptake and provide a conceptual basis for developing mechanism-based therapeutics for treating pathological conditions linked to de-regulated copper metabolism.
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