奥地利维也纳大学Alwin Köhler研究小组将一个灵活的篮状结构对接到核孔复合体的核心。该研究于2024年8月13日在线发表于国际一流学术期刊《自然—细胞生物学》。

通过整合基于AlphaFold的相互作用筛选、电镜和膜模板重构技术，研究人员揭示了核篮与核孔复合体（NPC）核心之间的膜锚定三部分连接。核篮亚单位Nup60含有三个相邻的短线性基序，这些基序连接了由柔性铰链中断的螺旋线段组成的平行同源二聚体Mlp1和Y复合体的Nup85亚单位。

研究人员在合成膜上重构了Y复合体•Nup60•Mlp1组装，并在体内验证了蛋白质接口。研究人员解释了基于短线性基序的蛋白质连接如何显著重塑NPC的结构和功能，推动了人们对NPC成分和构象异质性的理解。

据介绍，核篮附着在NPC的核质侧，将转录与mRNA质量控制和输出连接起来。核篮通过形成独特的RNA/蛋白质相互作用组，扩展了酿酒酵母中一部分NPC的功能。然而，核篮如何对接到NPC核心尚不清楚。

附：英文原文

Title: Docking a flexible basket onto the core of the nuclear pore complex

Author: Stankunas, Edvinas, Khler, Alwin

Issue&Volume: 2024-08-13

Abstract: The nuclear basket attaches to the nucleoplasmic side of the nuclear pore complex (NPC), coupling transcription to mRNA quality control and export. The basket expands the functional repertoire of a subset of NPCs in Saccharomyces cerevisiae by drawing a unique RNA/protein interactome. Yet, how the basket docks onto the NPC core remains unknown. By integrating AlphaFold-based interaction screens, electron microscopy and membrane-templated reconstitution, we uncovered a membrane-anchored tripartite junction between basket and NPC core. The basket subunit Nup60 harbours three adjacent short linear motifs, which connect Mlp1, a parallel homodimer consisting of coiled-coil segments interrupted by flexible hinges, and the Nup85 subunit of the Y-complex. We reconstituted the Y-complexNup60Mlp1 assembly on a synthetic membrane and validated the protein interfaces in vivo. Here we explain how a short linear motif-based protein junction can substantially reshape NPC structure and function, advancing our understanding of compositional and conformational NPC heterogeneity.

DOI: 10.1038/s41556-024-01484-x

Source: https://www.nature.com/articles/s41556-024-01484-x