Abstract
Amyloids are fibrillar protein aggregates with a cross-β structure and unusual features, including high resistance to detergent or protease treatment. More than two hundred different proteins with amyloid or amyloid-like properties are already known. Several examples of nucleoporins (e.g., yeast Nup49, Nup100, Nup116, and human NUP153) are supposed to form amyloid fibrils. In this study, we demonstrated an ability of the human NUP58 nucleoporin to form amyloid aggregates in vivo and in vitro. Moreover, we found two forms of NUP58 aggregates: oligomers and polymers stabilized by disulfide bonds. Bioinformatic analysis revealed that all known orthologs of this protein are potential amyloids which possess several regions with conserved ability to aggregation. The biological role of nucleoporin amyloid formation is debatable. We suggest that it is a rather abnormal process, which is characteristic for many proteins implicated in phase separation.
Highlights
Amyloids are fibrillar protein aggregates with cross-β structure, which can possess a number of other unusual features, including resistance to detergent and protease treatment and interaction with specific dyes (Congo Red and thioflavin T and S)
The nucleoporin protein family comprises more than three thousand proteins, most of which are essential for the formation of the nuclear pore complex (NPC) [9]
For the experiments in the C-DAG system, the E. coli strain VS39 [21] was transformed with target plasmids, and transformants were selected on LB medium supplemented with ampicillin and chloramphenicol at 37 °C [22]
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. The nucleoporin protein family comprises more than three thousand proteins, most of which are essential for the formation of the nuclear pore complex (NPC) [9]. These proteins can be divided into three groups: membrane, scaffold, and barrier nucleoporins. Human NUP58 protein is one of the most abundant barrier nucleoporins in NPC (48 molecules per complex) [11], but its Biomedicines 2021, 9, 1451. We analyzed the conservation of the amyloidogenic properties of its orthologs and the ability of this protein to form amyloid aggregates in vitro and in vivo
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