Solid-state NMR studies of metal-free SOD1 fibrillar structures |
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Authors: | Lucia Banci Olga Bla?evit? Francesca Cantini Jens Danielsson Lisa Lang Claudio Luchinat Jiafei Mao Mikael Oliveberg Enrico Ravera |
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Institution: | 1. Magnetic Resonance Center (CERM), University of Florence, Via L. Sacconi 6, 50019, Sesto Fiorentino, Italy 2. Department of Chemistry, University of Florence, Via della Lastruccia 3, 50019, Sesto Fiorentino, Italy 3. Fondazione Farmacogenomica FiorGen onlus, Via L. Sacconi 6, 50019, Sesto Fiorentino, Italy 4. Arrhenius Laboratories of Natural Sciences, Department of Biochemistry and Biophysics, Stockholm University, 106 91, Stockholm, Sweden 5. Goethe Universit?t, Max-von-Laue-Strasse 9, Biozentrum N202, 60438, Frankfurt am Main, Germany
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Abstract: | Copper–zinc superoxide dismutase 1 (SOD1) is present in the protein aggregates deposited in motor neurons of amyotrophic lateral sclerosis (ALS) patients. ALS is a neurodegenerative disease that can be either sporadic (ca. 90 %) or familial (fALS). The most widely studied forms of fALS are caused by mutations in the sequence of SOD1. Ex mortuo SOD1 aggregates are usually found to be amorphous. In vitro SOD1, in its immature reduced and apo state, forms fibrillar aggregates. Previous literature data have suggested that a monomeric SOD1 construct, lacking loops IV and VII, (apoSODΔIV–VII), shares the same fibrillization properties of apoSOD1, both proteins having the common structural feature of the central β-barrel. In this work, we show that structural information can be obtained at a site-specific level from solid-state NMR. The residues that are sequentially assignable are found to be located at the putative nucleation site for fibrillar species formation in apoSOD, as detected by other experimental techniques. |
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