5DLI

Corkscrew assembly of SOD1 residues 28-38

Summary for 5DLI

• Entry DOI: 10.2210/pdb5dli/pdb
• Descriptor: Superoxide dismutase [Cu-Zn], GLYCEROL, IODIDE ION, ... (4 entities in total)
• Functional Keywords: amyloid-related oligomer, unknown function
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 8
• Total formula weight: 10086.09

Authors

Sangwan, S.,Zhao, A.,Sawaya, M.R.,Eisenberg, D. (deposition date: 2015-09-05, release date: 2016-09-14, Last modification date: 2024-03-06)

Primary citation

Sangwan, S.,Zhao, A.,Adams, K.L.,Jayson, C.K.,Sawaya, M.R.,Guenther, E.L.,Pan, A.C.,Ngo, J.,Moore, D.M.,Soriaga, A.B.,Do, T.D.,Goldschmidt, L.,Nelson, R.,Bowers, M.T.,Koehler, C.M.,Shaw, D.E.,Novitch, B.G.,Eisenberg, D.S.
Atomic structure of a toxic, oligomeric segment of SOD1 linked to amyotrophic lateral sclerosis (ALS).
Proc. Natl. Acad. Sci. U.S.A., 114:8770-8775, 2017

PubMed Abstract: Fibrils and oligomers are the aggregated protein agents of neuronal dysfunction in ALS diseases. Whereas we now know much about fibril architecture, atomic structures of disease-related oligomers have eluded determination. Here, we determine the corkscrew-like structure of a cytotoxic segment of superoxide dismutase 1 (SOD1) in its oligomeric state. Mutations that prevent formation of this structure eliminate cytotoxicity of the segment in isolation as well as cytotoxicity of the ALS-linked mutants of SOD1 in primary motor neurons and in a (zebrafish) model of ALS. Cytotoxicity assays suggest that toxicity is a property of soluble oligomers, and not large insoluble aggregates. Our work adds to evidence that the toxic oligomeric entities in protein aggregation diseases contain antiparallel, out-of-register β-sheet structures and identifies a target for structure-based therapeutics in ALS.

PubMed: 28760994
DOI: 10.1073/pnas.1705091114

Experimental method

X-RAY DIFFRACTION (2.1 Å)