Solid-state NMR studies of metal-free SOD1 fibrillar structures

J Biol Inorg Chem. 2014 Jun;19(4-5):659-66. doi: 10.1007/s00775-014-1130-9. Epub 2014 Apr 10.

Abstract

Copper-zinc superoxide dismutase 1 (SOD1) is present in the protein aggregates deposited in motor neurons of amyotrophic lateral sclerosis (ALS) patients. ALS is a neurodegenerative disease that can be either sporadic (ca. 90%) or familial (fALS). The most widely studied forms of fALS are caused by mutations in the sequence of SOD1. Ex mortuo SOD1 aggregates are usually found to be amorphous. In vitro SOD1, in its immature reduced and apo state, forms fibrillar aggregates. Previous literature data have suggested that a monomeric SOD1 construct, lacking loops IV and VII, (apoSODΔIV-VII), shares the same fibrillization properties of apoSOD1, both proteins having the common structural feature of the central β-barrel. In this work, we show that structural information can be obtained at a site-specific level from solid-state NMR. The residues that are sequentially assignable are found to be located at the putative nucleation site for fibrillar species formation in apoSOD, as detected by other experimental techniques.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyotrophic Lateral Sclerosis / enzymology
  • Humans
  • Magnetic Resonance Spectroscopy / methods*
  • Superoxide Dismutase / chemistry*
  • Superoxide Dismutase / metabolism
  • Superoxide Dismutase-1

Substances

  • SOD1 protein, human
  • Superoxide Dismutase
  • Superoxide Dismutase-1