2VR8 : Crystal Structure of G85R ALS mutant of Human Cu,Zn Superoxide Dismutase (CuZnSOD) at 1.36 A resolution

  • Xiaohang Cao (Contributor)
  • Svetlana Antonyuk (Contributor)
  • Sai V. Seetharaman (Contributor)
  • Lisa J. Whitson (Contributor)
  • Alexander Bryan Taylor (Contributor)
  • Stephen P. Holloway (Contributor)
  • Richard W. Strange (Contributor)
  • Peter A. Doucette (Contributor)
  • Joan S. Valentine (Contributor)
  • Ashutosh Tiwari (Contributor)
  • Lawrence J. Hayward (Contributor)
  • Shelby Padua (Contributor)
  • Jeffrey A. Cohlberg (Contributor)
  • S. Samar Hasnain (Contributor)
  • P. John Hart (Contributor)

Dataset

Description

Experimental Technique/Method:X-RAY DIFFRACTION
Resolution:1.36
Classification:OXIDOREDUCTASE
Release Date:2008-04-08
Deposition Date:2008-03-28
Revision Date:2011-05-08#2011-07-13
Molecular Weight:32883.48
Macromolecule Type:Protein
Residue Count:308
Atom Site Count:2337
DOI:10.2210/pdb2vr8/pdb

Abstract:
Mutations in the gene encoding human copper-zinc superoxide dismutase (SOD1) cause a dominant form of the progressive neurodegenerative disease amyotrophic lateral sclerosis. Transgenic mice expressing the human G85R SOD1 variant develop paralytic symptoms concomitant with the appearance of SOD1-enriched proteinaceous inclusions in their neural tissues. The process(es) through which misfolding or aggregation of G85R SOD1 induces motor neuron toxicity is not understood. Here we present structures of the human G85R SOD1 variant determined by single crystal x-ray diffraction. Alterations in structure of the metal-binding loop elements relative to the wild type enzyme suggest a molecular basis for the metal ion deficiency of the G85R SOD1 protein observed in the central nervous system of transgenic mice and in purified recombinant G85R SOD1. These findings support the notion that metal-deficient and/or disulfide-reduced mutant SOD1 species contribute to toxicity in SOD1-linked amyotrophic lateral sclerosis.
Date made available2008
PublisherRCSB-PDB

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