Document Type
Article
Publication Date
2022
Keywords
Heslington Brain, Intrinsically Disordered Protein, Intrinsically Disordered Region, Binding-induced Folding, Disorder-to-order Transition
Digital Object Identifier (DOI)
https://doi.org/10.3390/biology11121704
Abstract
Proteomic analysis revealed the preservation of many proteins in the Heslington brain (which is at least 2600-year-old brain tissue uncovered within the skull excavated in 2008 from a pit in Heslington, Yorkshire, England). Five of these proteins—“main proteins”: heavy, medium, and light neurofilament proteins (NFH, NFM, and NFL), glial fibrillary acidic protein (GFAP), and myelin basic (MBP) protein—are engaged in the formation of non-amyloid protein aggregates, such as intermediate filaments and myelin sheath. We used a wide spectrum of bioinformatics tools to evaluate the prevalence of functional disorder in several related sets of proteins, such as the main proteins and their 44 interactors, all other proteins identified in the Heslington brain, as well as the entire human proteome (20,317 manually curated proteins), and 10,611 brain proteins. These analyses revealed that all five main proteins, half of their interactors and almost one third of the Heslington brain proteins are expected to be mostly disordered. Furthermore, most of the remaining Heslington brain proteins are expected to contain sizable levels of disorder. This is contrary to the expected substantial (if not complete) elimination of the disordered proteins from the Heslington brain. Therefore, it seems that the intrinsic disorder of NFH, NFM, NFL, GFAP, and MBP, their interactors, and many other proteins might play a crucial role in preserving the Heslington brain by forming tightly folded brain protein aggregates, in which different parts are glued together via the disorder-to-order transitions.
Rights Information
This work is licensed under a Creative Commons Attribution 4.0 License.
Was this content written or created while at USF?
Yes
Citation / Publisher Attribution
Biology, v. 11, issue 12, art. 1704
Scholar Commons Citation
Mohammed, Aaron S. and Uversky, Vladimir N., "Intrinsic Disorder as a Natural Preservative: High Levels of Intrinsic Disorder in Proteins Found in the 2600-year-old Human Brain" (2022). Molecular Medicine Faculty Publications. 1052.
https://digitalcommons.usf.edu/mme_facpub/1052
