Prevalence and Functionality of Intrinsic Disorder in Human FG-nucleoporins
Intrinsically disordered proteins, Intrinsically disordered regions, Nuclear-cytoplasmic transport, FG-Nups, Molecular recognition features, Interaction, Nucleoporins, Phase transitions, Fuzzy complexes
Digital Object Identifier (DOI)
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.
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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.