title: Dimerization, oligomerization, and aggregation of human amyotrophic lateral sclerosis copper/zinc superoxide dismutase 1 protein mutant forms in live cells.
abstract: More than 100 copper/zinc superoxide dismutase 1 (SOD1) genetic mutations have been characterized. These mutations lead to the death of motor neurons in ALS. In its native form, the SOD1 protein is expressed as a homodimer in the cytosol. In vitro studies have shown that SOD1 mutations impair the dimerization kinetics of the protein, and in vivo studies have shown that SOD1 forms aggregates in patients with familial forms of ALS. In this study, we analyzed WT SOD1 and 9 mutant (mt) forms of the protein by non-invasive fluorescence techniques. Using microscopic techniques such as fluorescence resonance energy transfer, fluorescence complementation, image-based quantification, and fluorescence correlation spectroscopy, we studied SOD1 dimerization, oligomerization, and aggregation. Our results indicate that SOD1 mutations lead to an impairment in SOD1 dimerization and, subsequently, affect protein aggregation. We also show that SOD1 WT and mt proteins can dimerize. However, aggregates are predominantly composed of SOD1 mt proteins.
authors.affiliation: From Neurodegeneration and Applied Microscopy, Institut Pasteur Korea, Seongnam-Si, Gyeonggi-Do 463-400, Republic of Korea.
authors.forename: Jiho
authors.initials: J
authors.lastname: Kim
authors.affiliation: From Neurodegeneration and Applied Microscopy, Institut Pasteur Korea, Seongnam-Si, Gyeonggi-Do 463-400, Republic of Korea.
authors.forename: Honggun
authors.initials: H
authors.lastname: Lee
authors.affiliation: From Neurodegeneration and Applied Microscopy, Institut Pasteur Korea, Seongnam-Si, Gyeonggi-Do 463-400, Republic of Korea.
authors.forename: Joo Hyun
authors.initials: JH
authors.lastname: Lee
authors.affiliation: From Neurodegeneration and Applied Microscopy, Institut Pasteur Korea, Seongnam-Si, Gyeonggi-Do 463-400, Republic of Korea.
authors.forename: Do-yoon
authors.initials: DY
authors.lastname: Kwon
authors.affiliation: From Neurodegeneration and Applied Microscopy, Institut Pasteur Korea, Seongnam-Si, Gyeonggi-Do 463-400, Republic of Korea.
authors.forename: Auguste
authors.initials: A
authors.lastname: Genovesio
authors.affiliation: From Neurodegeneration and Applied Microscopy, Institut Pasteur Korea, Seongnam-Si, Gyeonggi-Do 463-400, Republic of Korea.
authors.forename: Denis
authors.initials: D
authors.lastname: Fenistein
authors.affiliation: From Neurodegeneration and Applied Microscopy, Institut Pasteur Korea, Seongnam-Si, Gyeonggi-Do 463-400, Republic of Korea.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Ogier
authors.affiliation: From Neurodegeneration and Applied Microscopy, Institut Pasteur Korea, Seongnam-Si, Gyeonggi-Do 463-400, Republic of Korea.
authors.forename: Vincent
authors.initials: V
authors.lastname: Brondani
authors.affiliation: From Neurodegeneration and Applied Microscopy, Institut Pasteur Korea, Seongnam-Si, Gyeonggi-Do 463-400, Republic of Korea regis.grailhe@ip-korea.org.
authors.forename: Regis
authors.initials: R
authors.lastname: Grailhe
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology*; D031541:Fluorescence Resonance Energy Transfer; D057809:HEK293 Cells; D006801:Humans; D008099:Liver / Q000166:cytology / Q000201:enzymology*; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D018613:Microscopy, Confocal; D008958:Models, Molecular; D050505:Mutant Proteins / Q000737:chemistry / Q000235:genetics; D009154:Mutation; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D013050:Spectrometry, Fluorescence; D013482:Superoxide Dismutase / Q000737:chemistry* / Q000235:genetics*; D000072105:Superoxide Dismutase-1
chemical_list: D008164:Luminescent Proteins; D050505:Mutant Proteins; C000606290:SOD1 protein, human; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1
keywords: Fluorescence Resonance Energy Transfer (FRET); Fluorescence correlation Spectroscopy; Mutant; Protein Aggregation; Protein Misfolding; Superoxide Dismutase (SOD)