1OZT : Crystal Structure of apo-H46R Familial ALS Mutant human Cu,Zn Superoxide Dismutase (CuZnSOD) to 2.5A resolution

  • Jennifer Stine Elam (Contributor)
  • Alexander Bryan Taylor (Contributor)
  • Richard W. Strange (Contributor)
  • Svetlana Antonyuk (Contributor)
  • Peter A. Doucette (Contributor)
  • Jorge A. Rodriguez (Contributor)
  • S. Samar Hasnain (Contributor)
  • Lawrence J. Hayward (Contributor)
  • Joan S. Valentine (Contributor)
  • Todd O. Yeates (Contributor)
  • P. John Hart (Contributor)



Experimental Technique/Method:X-RAY DIFFRACTION
Release Date:2003-05-27
Deposition Date:2003-04-09
Revision Date:2008-04-29#2011-07-13
Molecular Weight:126772.86
Macromolecule Type:Protein
Residue Count:1224
Atom Site Count:7966

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.
Date made available2003

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