| http://purl.uniprot.org/citations/19828437 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/19828437 | http://www.w3.org/2000/01/rdf-schema#comment | "Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease linked to the misfolding of Cu/Zn superoxide dismutase (SOD1). ALS-related defects in SOD1 result in a gain of toxic function that coincides with aberrant oligomerization. The structural events triggering oligomerization have remained enigmatic, however, as is the case in other protein-misfolding diseases. Here, we target the critical conformational change that defines the earliest step toward aggregation. Using nuclear spin relaxation dispersion experiments, we identified a short-lived (0.4 ms) and weakly populated (0.7%) conformation of metal-depleted SOD1 that triggers aberrant oligomerization. This excited state emanates from the folded ground state and is suppressed by metal binding, but is present in both the disulfide-oxidized and disulfide-reduced forms of the protein. Our results pinpoint a perturbed region of the excited-state structure that forms intermolecular contacts in the earliest nonnative dimer/oligomer. The conformational transition that triggers oligomerization is a common feature of WT SOD1 and ALS-associated mutants that have widely different physicochemical properties. But compared with WT SOD1, the mutants have enhanced structural distortions in their excited states, and in some cases slightly higher excited-state populations and lower kinetic barriers, implying increased susceptibility to oligomerization. Our results provide a unified picture that highlights both (i) a common denominator among different SOD1 variants that may explain why diverse mutations cause the same disease, and (ii) a structural basis that may aid in understanding how different mutations affect disease propensity and progression."xsd:string |
| http://purl.uniprot.org/citations/19828437 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.0907387106"xsd:string |
| http://purl.uniprot.org/citations/19828437 | http://purl.uniprot.org/core/author | "Teilum K."xsd:string |
| http://purl.uniprot.org/citations/19828437 | http://purl.uniprot.org/core/author | "Schulz E."xsd:string |
| http://purl.uniprot.org/citations/19828437 | http://purl.uniprot.org/core/author | "Akke M."xsd:string |
| http://purl.uniprot.org/citations/19828437 | http://purl.uniprot.org/core/author | "Oliveberg M."xsd:string |
| http://purl.uniprot.org/citations/19828437 | http://purl.uniprot.org/core/author | "Smith M.H."xsd:string |
| http://purl.uniprot.org/citations/19828437 | http://purl.uniprot.org/core/author | "Christensen L.C."xsd:string |
| http://purl.uniprot.org/citations/19828437 | http://purl.uniprot.org/core/author | "Solomentsev G."xsd:string |
| http://purl.uniprot.org/citations/19828437 | http://purl.uniprot.org/core/date | "2009"xsd:gYear |
| http://purl.uniprot.org/citations/19828437 | http://purl.uniprot.org/core/name | "Proc Natl Acad Sci U S A"xsd:string |
| http://purl.uniprot.org/citations/19828437 | http://purl.uniprot.org/core/pages | "18273-18278"xsd:string |
| http://purl.uniprot.org/citations/19828437 | http://purl.uniprot.org/core/title | "Transient structural distortion of metal-free Cu/Zn superoxide dismutase triggers aberrant oligomerization."xsd:string |
| http://purl.uniprot.org/citations/19828437 | http://purl.uniprot.org/core/volume | "106"xsd:string |
| http://purl.uniprot.org/citations/19828437 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/19828437 |
| http://purl.uniprot.org/citations/19828437 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/19828437 |
| http://purl.uniprot.org/uniprot/P00441#attribution-9935C65046723777E81395C9DED1817E | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/19828437 |
| http://purl.uniprot.org/uniprot/#_A1YYW4-mappedCitation-19828437 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/19828437 |
| http://purl.uniprot.org/uniprot/#_P00441-mappedCitation-19828437 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/19828437 |
| http://purl.uniprot.org/uniprot/#_L8E9E6-mappedCitation-19828437 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/19828437 |
| http://purl.uniprot.org/uniprot/#_X5CHU1-mappedCitation-19828437 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/19828437 |
| http://purl.uniprot.org/uniprot/#_X5CN18-mappedCitation-19828437 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/19828437 |
| http://purl.uniprot.org/uniprot/#_W8Q444-mappedCitation-19828437 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/19828437 |
| http://purl.uniprot.org/uniprot/#_X5CQ60-mappedCitation-19828437 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/19828437 |