Change search
ReferencesLink to record
Permanent link

Direct link
Structural basis of the iron storage function of frataxin from single-particle reconstruction of the iron-loaded oligomer
KTH, School of Technology and Health (STH), Structural Biotechnology.
Show others and affiliations
2008 (English)In: Biochemistry, ISSN 0006-2960, E-ISSN 1520-4995, Vol. 47, no 17, 4948-4954 p.Article in journal (Refereed) Published
Abstract [en]

The mitochondrial protein frataxin plays a central role in mitochondrial iron homeostasis, and frataxin deficiency is responsible for Friedreich ataxia, a neurodegenerative and cardiac disease that affects 1 in 40000 children. Here we present a single-particle reconstruction from cryoelectron microscopic images of iron-loaded 24-subunit oligomeric frataxin particles at 13 and 17 angstrom resolution. Computer-aided classification of particle images showed heterogeneity in particle size, which was hypothesized to result from gradual accumulation of iron within the core structure. Thus, two reconstructions were created from two classes of particles with iron cores of different sizes. The reconstructions show the iron core of frataxin for the first time. Compared to the previous reconstruction of iron-free particles from negatively stained images, the higher resolution of the present reconstruction allowed a more reliable analysis of the overall three-dimensional structure of the 24-meric assembly. This was done after docking the X-ray structure of the frataxin trimer into the EM reconstruction. The structure revealed a close proximity of the suggested ferroxidation sites of different monomers to the site proposed to serve in iron nucleation and mineralization. The model also assigns a new role to the N-terminal helix of frataxin in controlling the channel at the 4-fold axis of the 24-subunit oligomer. The reconstructions show that, together with some common features, frataxin has several unique features which distinguish it from ferritin. These include the overall organization of the oligomers, the way they are stabilized, and the mechanisms of iron core nucleation.

Place, publisher, year, edition, pages
2008. Vol. 47, no 17, 4948-4954 p.
Keyword [en]
yeast frataxin, saccharomyces-cerevisiae, friedreich ataxia, protein, ferrochelatase, ferritin, binding, visualization, biosynthesis, microscopy
National Category
Biochemistry and Molecular Biology
URN: urn:nbn:se:kth:diva-17468DOI: 10.1021/bi800052mISI: 000255164700010ScopusID: 2-s2.0-42449093713OAI: diva2:335512
QC 20100525Available from: 2010-08-05 Created: 2010-08-05 Last updated: 2012-04-04Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textScopusBiochemistry

Search in DiVA

By author/editor
Elmlund, HansHebert, HansLindahl, Martin
By organisation
Structural Biotechnology
In the same journal
Biochemistry and Molecular Biology

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 30 hits
ReferencesLink to record
Permanent link

Direct link