Zapraszamy na wykład profesora Salama Al-Karadaghiego z Uniwersytetu w Lund (Szwecja), który odbędzie się w poniedziałek 27 kwietnia. Wykład został zatytułowany: „Metal-dependent oligomerization and the metal-chaperone
function of frataxin: Insights from integrated structural biology approach”. Wykład odbędzie się o godz 11:00 w Sali Rady Wydziału (pokój 151B), I piętro budynku Wydziału Biologii i Biotechnologii UMCS, ul Akademicka 19.
Abstrakt wykładu:
Metal-dependent oligomerization and the metal-chaperone function of frataxin:
Insights from integrated structural biology approach
Salam Al-Karadaghi, Dept. of Biochemistry & Structural Biology, Lund
University, Sweden
Frataxin a mitochondrial protein, which has been linked to the
neurodegenerative disease Friedreich’s ataxia, is known to perform key
functions in iron storage, delivery and detoxification in mitochondria. Using
X-ray crystallography, single-particle electron microscopy and small-angle
X-ray scattering (SAXS), we have studied metal-dependent oligomerisation of
frataxin and compared oligomerization induced by the non-physiological metal
Co2+ with that induced by Fe2+ (1-4).
The oligomeric structures show that in yeast trimers are the basic building
blocks of higher-order oligomers, while for the bacterial homologue of
frataxin a tetramer appears to form the basis for formation of higher order
oligomers. The studies provide the basis for understanding the mechanisms of
metal-induced frataxin oligomer assembly and give new insights into frataxin
function in iron storage and detoxification. They also provide an insight into
the interplay between frataxin and other proteins, for which frataxin
functions as a metal chaperone. The structural details of the model of the
complex of frataxin with ferrochelatase, the terminal enzyme of heme
synthesis, will be discussed.
1. Karlberg, T., Schagerlöf, U., Gakh, O., Park, S., Ryde, U., Lindahl, M.,
Leath, K., Garman, E., Isaya, G. & Al-Karadaghi, S. (2006). Structure 14,
1535-15646.
2. Schagerlöf, U., Elmlund, H., Gakh, O., Nordlund, G., Hebert, H., Lindahl,
M., Isaya, G. and Al-Karadaghi, S. (2008). Biochemistry 47, 4948-4954.
3. Söderberg C.A.G., Shkumatov A.V., Rajan S., Gakh O., Svergun D.I., Isaya G.
and Al-Karadaghi S. (2011). J. Mol. Biol. 414, 783-797.
4. Söderberg, CAG, Rajan, S, Shkumatov, AV, Gakh, O, Schaefer, S., Ahlgren,
E-C, Svergun, DI, Isaya, G and Al-Karadaghi, S. (2013). J Biol Chem, 288,
8156-8167.
