Structural Insights into the Acquisition and Storage of Iron
Author
Summary, in English
In 1999, a membrane bound ferric reductase called FRO2 was identified in A. thaliana. This protein enables the plant to acquire bioavailable iron from mineral soil When this project was initiated no structural information was available for FRO2 or any other known homologue. We have been able to establish the membrane topology for FRO2 and also to indicate the topology for several other homologous proteins by combining sequence alignment with our results for FRO2. Sequential alignment of the water-soluble flavin-binding domain of FRO2 and structural alignment of other members of the same protein family enable us to present a prediction of the tertiary structure of this domain. Indications of a conserved complex formation between FRO2 and the membrane-bound iron transporter IRT1 are also presented together with a proposed arrangement of the individual subunits in the complex.
The main iron chaperone in mitochondria is called frataxin. Frataxin has recently been shown to perform the dual function of delivering bioavailable Fe(II) to several iron-chelating proteins and maintaining mitochondrial iron homeostasis by the detoxification of surplus iron. Dysfunction of the protein is closely linked to a neurodegenerative disease known as Freidrich's ataxia. The structure of the trimeric Y73A yeast frataxin mutant with bound iron indicates that the trimer is the basic functional unit that delivers Fe(II) to iron requiring processes inside the mitochondria. The 24-oligomeric Y73A apo structure provides an initial scaffold for the storage of iron inside the hollow structure. The gradually increasing iron cores in the pre-assembled iron loaded Y73A mutant of 24-oligomeric yeast frataxin structures provide a new starting point for deducing the initiation of iron accumulation inside the protein structure. This also strongly suggests that the pre-assembled Y73A mutant of yeast frataxin is an acceptable model for the human frataxin system.
Department/s
Publishing year
2007
Language
English
Document type
Dissertation
Publisher
Department of Molecular Biophysics, Lund University
Topic
- Biological Sciences
Keywords
- Strukturkemi
- Molecular biophysics
- Molekylär biofysik
- Structure chemistry
- single particle
- ferric reductase
- human phagocyte superoxide-generating NADPH oxidase
- frataxin
- cryo electron microscopy
- FRO2
- iron homeostasis
- iron acquisition
Status
Published
Supervisor
- Hans Hebert
ISBN/ISSN/Other
- ISBN: 978-91-7422-156-5
Defence date
4 May 2007
Defence time
10:15
Defence place
Lund University Getingevägen 60 Center for Chemistry & Chemical Engineering Lecture hall A
Opponent
- Simon Andrews (Professor)