Danilov Lavrentii G, Moskalenko Svetlana E, Matveenko Andrew G, Sukhanova Xenia V, Belousov Mikhail V, Zhouravleva Galina A, Bondarev Stanislav A
Department of Genetics and Biotechnology, St. Petersburg State University, 199034 St. Petersburg, Russia.
St. Petersburg Branch, Vavilov Institute of General Genetics, Russian Academy of Sciences, 199034 St. Petersburg, Russia.
Biomedicines. 2021 Oct 13;9(10):1451. doi: 10.3390/biomedicines9101451.
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.
淀粉样蛋白是具有交叉β结构和异常特性的纤维状蛋白质聚集体，包括对去污剂或蛋白酶处理具有高度抗性。目前已经知道有两百多种具有淀粉样或类淀粉样特性的不同蛋白质。几种核孔蛋白（例如酵母中的Nup49、Nup100、Nup116以及人类的NUP153）被认为会形成淀粉样纤维。在本研究中，我们证明了人类核孔蛋白NUP58在体内和体外形成淀粉样聚集体的能力。此外，我们发现了两种形式的NUP58聚集体：寡聚体和由二硫键稳定的聚合物。生物信息学分析表明，该蛋白质的所有已知直系同源物都是潜在的淀粉样蛋白，它们拥有几个具有保守聚集能力的区域。核孔蛋白形成淀粉样蛋白的生物学作用存在争议。我们认为这是一个相当异常的过程，许多参与相分离的蛋白质都具有这一特征。
