For the first time, the three dimensional structure of the protein that is essential for iron import into cells, has been elucidated. Biochemists of the University of Zurich have paved the way towards a better understanding of iron metabolism. The results also provide a basis for novel approaches to treat iron-related metabolic diseases.
Iron is the most abundant trace element in humans. As a cofactor of certain proteins, it plays an essential role in oxygen transport and metabolism. Due to the major im-portance of iron in a wide variety of cellular processes, and the harm caused by its uncontrolled accumulation in the body, its uptake and storage is strictly regulated.
Structure of the iron transport-protein. A zoom into the iron binding-site (right) shows the interaction of the bound ion with conserved amino-acids. UZH
In mammals, iron is imported into cells by the membrane transport protein DMT1. Mu-tations of DMT1, which affect its transport properties, lead to iron-related metabolic disorders such as anemia and the iron storage disease hemochromatosis.
Ines Ehrnstorfer, a PhD student in the group of Professor Raimund Dutzler at the Department of Biochemistry of the University of Zurich, and her colleagues, have determined the first structure of an iron transport protein. Their work was published in the scientific journal Nature Structural and Molecular Biology. Based on these re-sults the researchers were able to explain why DMT1 binds the divalent metal ions iron and manganese (Fe2+ and Mn2+), but not calcium (Ca2+) – in spite of the latter being several orders of magnitude more abundant.
Moleclar basis for selective ion transport
To unravel the structural basis for this ion selectivity, Ines Ehrnstorfer has deter-mined the structure of a close bacterial homologue of DMT1 by X-ray crystallography. The transport protein contains an ion binding site located at the center of the mem-brane that is composed of conserved amino acids.
“One of these amino acids, a me-thionine, only interacts with transition-metal ions, but not with Ca2+”, explains Ehrn-storfer. The study also shows that mutations in the binding site weaken ion binding and transport in both the bacterial homologue and human DMT1.
“The results thus reveal how transition-metal ions such as iron are selectively trans-ported across the membrane, and they provide a basis for the development of spe-cific inhibitors of DMT1 for the treatment of iron storage diseases,” says the re-searcher.
The project was funded by the Swiss National Science Foundation through the National Center of Competence in Research (NCCR) TransCure.
Ines A Ehrnstorfer, et al. Crystal structure of a SLC11 (NRAMP) transporter reveals the basis for transition-metal ion transport. Nature Structural and Molecular Biology, advanced online publication October 19 2014. Doi: 10.1038/nsmb.2904
Prof. Raimund Dutzler
Department of Biochemistry
University of Zurich
Tel.: +41 44 635 65 50
University of Zurich
Tel.: +41 44 634 44 39
Bettina Jakob | Universität Zürich
Climate Impact Research in Hannover: Small Plants against Large Waves
17.08.2018 | Leibniz Universität Hannover
First transcription atlas of all wheat genes expands prospects for research and cultivation
17.08.2018 | Leibniz-Institut für Pflanzengenetik und Kulturpflanzenforschung
New design tool automatically creates nanostructure 3D-print templates for user-given colors
Scientists present work at prestigious SIGGRAPH conference
Most of the objects we see are colored by pigments, but using pigments has disadvantages: such colors can fade, industrial pigments are often toxic, and...
Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...
Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.
When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...
Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.
Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....
Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.
Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...
17.08.2018 | Event News
08.08.2018 | Event News
27.07.2018 | Event News
17.08.2018 | Physics and Astronomy
17.08.2018 | Information Technology
17.08.2018 | Life Sciences