1OEZ

Zn His46Arg mutant of Human Cu, Zn Superoxide Dismutase

Summary for 1OEZ

• Entry DOI: 10.2210/pdb1oez/pdb
• Related: 1AZV 1BA9 1DSW 1FUN 1HL4 1HL5 1KMG 1L3N 1MFM 1N18 1N19 1OZT 1OZU 1SOS 1SPD 4SOD
• Descriptor: SUPEROXIDE DISMUTASE [CU-ZN], ZINC ION, SULFATE ION, ... (4 entities in total)
• Functional Keywords: oxidoreductase, human cu, zn superoxide dismutase
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Cytoplasm: P00441
• Total number of polymer chains: 4
• Total formula weight: 64032.32

Authors

Strange, R.W.,Antonyuk, S.,Hough, M.A.,Doucette, P.,Rodriguez, J.,Elam, J.S.,Hart, P.J.,Hayward, L.J.,Valentine, J.S.,Hasnain, S.S. (deposition date: 2003-04-02, release date: 2003-05-29, Last modification date: 2024-10-23)

Primary citation

Elam, J.S.,Taylor, A.B.,Strange, R.W.,Antonyuk, S.,Doucette, P.,Rodriguez, J.,Hasnain, S.S.,Hayward, L.J.,Valentine, J.S.,Yeates, T.O.,Hart, P.J.
Amyloid-Like Filaments and Water-Filled Nanotubes Formed by Sod1 Mutant Proteins Linked to Familial Als
Nat.Struct.Biol., 10:461-, 2003

PubMed Abstract: Mutations in the SOD1 gene cause the autosomal dominant, neurodegenerative disorder familial amyotrophic lateral sclerosis (FALS). In spinal cord neurons of human FALS patients and in transgenic mice expressing these mutant proteins, aggregates containing FALS SOD1 are observed. Accumulation of SOD1 aggregates is believed to interfere with axonal transport, protein degradation and anti-apoptotic functions of the neuronal cellular machinery. Here we show that metal-deficient, pathogenic SOD1 mutant proteins crystallize in three different crystal forms, all of which reveal higher-order assemblies of aligned beta-sheets. Amyloid-like filaments and water-filled nanotubes arise through extensive interactions between loop and beta-barrel elements of neighboring mutant SOD1 molecules. In all cases, non-native conformational changes permit a gain of interaction between dimers that leads to higher-order arrays. Normal beta-sheet-containing proteins avoid such self-association by preventing their edge strands from making intermolecular interactions. Loss of this protection through conformational rearrangement in the metal-deficient enzyme could be a toxic property common to mutants of SOD1 linked to FALS.

PubMed: 12754496
DOI: 10.1038/NSB935

Experimental method

X-RAY DIFFRACTION (2.15 Å)