Teimer Roman, Kosinski Jan, von Appen Alexander, Beck Martin, Hurt Ed
Biochemistry Center of Heidelberg University (BZH), Im Neuenheimer Feld 328, 69120, Heidelberg, Germany.
Structural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL), Meyerhofstraße 1, 69117, Heidelberg, Germany.
Nat Commun. 2017 Oct 24;8(1):1107. doi: 10.1038/s41467-017-01160-9.
Nucleocytoplasmic transport occurs through nuclear pore complexes (NPCs), which are formed from multiple copies of ~30 different nucleoporins (Nups) and inserted into the double nuclear membrane. Many of these Nups are organized into subcomplexes, of which the Y-shaped Nup84 complex is the major constituent of the nuclear and cytoplasmic rings. The Nup82-Nup159-Nsp1 complex is another module that, however, is only assembled into the cytoplasmic ring. By means of crosslinking mass spectrometry, biochemical reconstitution, and molecular modeling, we identified a short linear motif in the unstructured N-terminal region of Chaetomium thermophilum Nup145C, a subunit of the Y-complex, that is sufficient to recruit the Nup82 complex, but only in its assembled state. This finding points to a more general mechanism that short linear motifs in structural Nups can act as sensors to cooperatively connect pre-assembled NPC modules, thereby facilitating the formation and regulation of the higher-order NPC assembly.
核质运输通过核孔复合体（NPC）进行，核孔复合体由约30种不同核孔蛋白（Nup）的多个拷贝形成，并插入双层核膜中。许多这些核孔蛋白被组织成亚复合体，其中Y形的Nup84复合体是核环和胞质环的主要成分。Nup82-Nup159-Nsp1复合体是另一个模块，但它仅组装到胞质环中。通过交联质谱、生化重构和分子建模，我们在嗜热毛壳菌Nup145C（Y复合体的一个亚基）的无结构N端区域鉴定出一个短线性基序，该基序足以招募Nup82复合体，但仅在其组装状态下。这一发现指向一种更普遍的机制，即结构性核孔蛋白中的短线性基序可作为传感器，协同连接预组装的NPC模块，从而促进高阶NPC组装的形成和调节。
