Prevalence and Functionality of Intrinsic Disorder in Human FG-nucleoporins
Document Type
Article
Publication Date
2021
Keywords
Intrinsically disordered proteins, Intrinsically disordered regions, Nuclear-cytoplasmic transport, FG-Nups, Molecular recognition features, Interaction, Nucleoporins, Phase transitions, Fuzzy complexes
Digital Object Identifier (DOI)
https://doi.org/10.1016/j.ijbiomac.2021.01.218
Abstract
The nuclear-cytoplasmic transport of biomolecules is assisted by the nuclear pores composed of evolutionarily conserved proteins termed nucleoporins (Nups). The central Nups, characterized by multiple FG-repeats, are highly dynamic and contain a high level of intrinsically disordered regions (IDPRs). FG-Nups bind several protein partners and play critical roles in molecular interactions and the regulation of cellular functions through their IDPRs. In the present study, we performed a multiparametric bioinformatics analysis to characterize the prevalence and functionality of IDPRs in human FG-Nups. These analyses revealed that the sequence of all FG-Nups contained >50% IDPRs (except Nup54 and Nup358). Nup98, Nup153, and POM121 were extremely disordered with ~80% IDPRs. The functional disorder-based binding regions in the FG-Nups were identified. The phase separation behavior of FG-Nups indicated that all FG-Nups have the potential to undergo liquid-to-liquid phase separation that could stabilize their liquid state. The inherent structural flexibility in FG-Nups is mechanistically and functionally advantageous. Since certain FG-Nups interact with disease-relevant protein aggregates, their complexes can be exploited for drug design. Furthermore, consideration of the FG-Nups from the intrinsic disorder perspective provides critical information that can guide future experimental studies to uncover novel pathways associated with diseases linked with protein misfolding and aggregation.
Was this content written or created while at USF?
Yes
Citation / Publisher Attribution
International Journal of Biological Macromolecules, v. 175, p. 156-170
Scholar Commons Citation
Lyngdoh, Denzelle Lee; Nag, Niharika; Uversky, Vladimir N.; and Tripathi, Timir, "Prevalence and Functionality of Intrinsic Disorder in Human FG-nucleoporins" (2021). Molecular Medicine Faculty Publications. 201.
https://digitalcommons.usf.edu/mme_facpub/201
