Subunit asymmetry in the three-dimensional structure of a human CuZnSOD mutant found in familial amyotrophic lateral sclerosis

P. John Hart, Hongbin Liu, Matteo Pellegrini, Aram M. Nersissian, Edith B. Gralla, Joan S. Valentine, David Eisenberg

Research output: Contribution to journalArticlepeer-review

102 Scopus citations

Abstract

The X-ray crystal structure of a human copper/zinc superoxide dismutase mutant (G37R CuZnSOD) found in some patients with the inherited form of Lou Gehrig's disease (FALS) has been determined to 1.9 Å resolution. The two SOD subunits have distinct environments in the crystal and are different in structure at their copper binding sites. One subunit (subunit(intact)) shows a four-coordinate ligand geometry of the copper ion, whereas the other subunit (subunit(broken)) shows a three-coordinate geometry of the copper ion. Also, subunit(intact) displays higher atomic displacement parameters for backbone atoms (= 30 ± 10 Å2) than subunit(broken) (= 24 ± 11 Å2). This structure is the first CuZnSOD to show large differences between the two subunits. Factors that may contribute to these differences are discussed and a possible link of a looser structure to FALS is suggested.

Original languageEnglish (US)
Pages (from-to)545-555
Number of pages11
JournalProtein Science
Volume7
Issue number3
DOIs
StatePublished - Mar 1998

Keywords

  • Amyotrophic lateral sclerosis
  • Apoptosis
  • Lou Gehrig's disease
  • Motor neuron
  • Neurodegeneration
  • Oxidative damage
  • Superoxide dismutase
  • X-ray crystallography

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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