Intrinsic Disorder in Proteins Involved in Amyotrophic Lateral Sclerosis
Document Type
Article
Publication Date
2017
Keywords
Neurodegeneration, Amyotrophic lateral sclerosis, SOD1, TDP-43, FUS, Intrinsically disordered proteins, Protein–protein interactions, Posttranslational modifications, Binding-induced folding, Polymorphism, Protein structure, Protein function
Digital Object Identifier (DOI)
https://doi.org/10.1007/s00018-016-2416-6
Abstract
Five structurally and functionally different proteins, an enzyme superoxide dismutase 1 (SOD1), a TAR-DNA binding protein-43 (TDP-43), an RNA-binding protein FUS, a cofilin-binding protein C9orf72, and polypeptides generated as a result of its intronic hexanucleotide expansions, and to lesser degree actin-binding profilin-1 (PFN1), are considered to be the major drivers of amyotrophic lateral sclerosis. One of the features common to these proteins is the presence of significant levels of intrinsic disorder. The goal of this study is to consider these neurodegeneration-related proteins from the intrinsic disorder perspective. To this end, we employed a broad set of computational tools for intrinsic disorder analysis and conducted intensive literature search to gain information on the structural peculiarities of SOD1, TDP-43, FUS, C9orf72, and PFN1 and their intrinsic disorder predispositions, and the roles of intrinsic disorder in their normal and pathological functions.
Was this content written or created while at USF?
Yes
Citation / Publisher Attribution
Cellular and Molecular Life Sciences, v. 74, p. 1297-1318
Scholar Commons Citation
Santamaria, Nikolas; Alhothali, Marwa; Alfonso, Maria Harreguy; Breydo, Leonid; and Uversky, Vladimir N., "Intrinsic Disorder in Proteins Involved in Amyotrophic Lateral Sclerosis" (2017). Molecular Medicine Faculty Publications. 317.
https://digitalcommons.usf.edu/mme_facpub/317
