Structure and mechanism of mammalian ferroportin

哺乳动物铁转运蛋白的结构和机制

• 批准号: 10605203
• 负责人: Yaping Pan
• 金额: $ 40万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10605203
• 关键词: Affinity; Binding; Binding Sites; Biological Assay; Cells; Complex; Cryoelectron Microscopy; Endocytosis Induction; Enzymes; Fab Immunoglobulins; Family; Foundations; Future; Genus Tarsius; Goals; Hemochromatosis; Hemoglobin; Hereditary Disease; Homeostasis; Human; Ion Transport; Ions; Iron; Iron Metabolism Disorders; Iron Overload; Iron deficiency anemia; Lipids; Liver; Mammals; Maps; Measures; Mediating; Metal Ion Binding; Metals; Molecular Conformation; Monoclonal Antibodies; Mutation; Myoglobin; Nutrient; Oxidation-Reduction; Regulation; Resolution; Role; Side; Site; Solid; Solvents; Structure; Symptoms; Trace Elements; Visualization; antiporter; extracellular; hepcidin; improved; indexing; inhibitor; iron deficiency; member; metal transporting protein 1; nanodisk; peptide hormone; reconstitution; small molecule; small molecule inhibitor; solute; therapeutic target; three dimensional structure

Project Summary: Ferroportin is the only iron exporter in humans. Mutations in ferroportin cause hemochromatosis. Ferrorpotin is regulated by a peptide hormone hepcidin, which is produced in the liver and inhibits the activity of ferrorportin by inducing endocytosis and by direct inhibition of ferroportin activity. The FPN-hepcidin axis is a potential therapeutic target for normalizing iron homeostasis in hemochromatosis. However, very little is known about how ferroportin recognizes and transport iron and how it interacts with hepcidin. In this study, I will combine structural and functional analyses to understand the mechanism of iron transport and inhibition in ferroportin at the atomic resolution.

项目概要： Ferroportin是人类唯一的铁输出者。铁转运蛋白的突变导致 血色病Ferrorpotin受肽激素hepcidin调节， 在肝脏中产生，并通过诱导内吞作用抑制铁蛋白的活性， 通过直接抑制膜铁转运蛋白活性。FPN-hepcidin轴是一种潜在的治疗药物， 用于使血色病中铁稳态正常化的靶点。然而，很少有 我们知道膜铁转运蛋白如何识别和转运铁，以及它如何与 铁调素在这项研究中，我将联合收割机的结构和功能分析相结合，以了解 在原子分辨率下探讨膜铁转运蛋白的铁转运和抑制机制。

项目成果

Structural basis of ferroportin inhibition by minihepcidin PR73.

• DOI: 10.1371/journal.pbio.3001936
• 发表时间: 2023-01
• 期刊: PLoS biology
• 影响因子: 9.8