Biochemical Characterization of the Core Structure of α-Synuclein Filaments*
By H. Miake, H. Mizusawa, T. Iwatsubo, M. Hasegawa. Journal of Biological Chemistry, 2002
229 citations recorded by the source corpus.
Intracellular filamentous aggregates comprised of α-synuclein such as Lewy bodies and glial cytoplasmic inclusions are the defining hallmarks of a subset of neurodegenerative diseases including Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. We have analyzed biochemical and structural properties of α-synuclein filaments assembled in vitro or extracted from brains of patients with multiple system atrophy and found that both types of filaments are insoluble to detergents and partially resistant to proteinase K digestion. Immunoelectron microscopy and immunoblot analysis showed that both amino and carboxyl termini of α-synuclein in in vitro assembled filaments were degraded by proteinase K treatment, whereas the central portion of α-synuclein is resistant to proteinase K and retains filamentous structures. Protein sequencing and mass spectrometric analyses of the proteinase K-resistant, minimal fragment of 7 kDa revealed that amino acid residues 31–109 of α-synuclein constitute the core unit of the filaments. These observations suggest that the central half of the α-synuclein polypeptide, containing five tandem repeats as well as a part of the carboxyl-terminal acidic region, forms the core structure of α-synuclein filaments, which is coated by the amino- and carboxyl-terminal portions at the periphery.
Subfields: Complementary and alternative medicine, Neurology
View Paper: https://www.semanticscholar.org/paper/d8b7bebc175415a7f1fbff40d5b9f60c83d97aee
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Citations in the corpus
- Direct Observation of the Interconversion of Normal and Toxic Forms of α-Synuclein (2012, background): “As resistance to proteolytic, and specifically proteinase K, digestion has been found generally to correlate with the degree of persistent structure and b sheet content of aggregated species (Kocisko et al., 1995; Miake et al., 2002; Nordstedt et al., 1994), our results strongly suggest that type-A ”
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