Systematically perturbed folding patterns of amyotrophic lateral sclerosis (ALS)-associated SOD1 mutants
2005 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, Vol. 102, no 28, 9754-9 p.Article in journal (Refereed) Published
Amyotrophic lateral sclerosis is a neurodegenerative syndrome associated with 114 mutations in the gene encoding the cytosolic homodimeric enzyme Cu/Zn superoxide dismutase (SOD). In this article, we report that amyotrophic lateral sclerosis-associated SOD mutations with distinctly different disease progression can be rationalized in terms of their folding patterns. The mutations are found to perturb the protein in multiple ways; they destabilize the precursor monomers (class 1), weaken the dimer interface (class 2), or both at the same time (class 1 + 2). A shared feature of the mutational perturbations is a shift of the folding equilibrium toward poorly structured SOD monomers. We observed a link, coupled to the altered folding patterns, between protein stability, net charge, and survival time for the patients carrying the mutations.
Place, publisher, year, edition, pages
National Academy of Sciences , 2005. Vol. 102, no 28, 9754-9 p.
neurodegenerative disease, protein stability
IdentifiersURN: urn:nbn:se:umu:diva-14675DOI: 10.1073/pnas.0501957102OAI: oai:DiVA.org:umu-14675DiVA: diva2:154347