May 2025 - Edvinas Stankunas

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Edvinas Stankunas, MSc

MedUni Wien RESEARCHER OF THE MONTH May 2025

Nuclear pore complex (NPC) is the sole gateway within the nuclear envelope mediating bidirectional macromolecular transport of cargos between the cytoplasm and nucleus [1-2]. The nucleoplasmic face of the NPC is decorated by a fishtrap-like structure, known as the nuclear basket, which couples transcription to mRNA quality control and export [3]. The basket expands the functional repertoire of a subset of NPCs in Saccharomyces cerevisiae by drawing a unique RNA/protein interactome [4]. Yet, how the basket docks onto the NPC core remained unknown. By integrating AlphaFold-based interaction screens, electron microscopy and membrane-templated reconstitution, a membrane-anchored tripartite junction between basket and NPC core has been uncovered [5]. 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 [5]. The study sheds light how a short linear motif-based protein junction can substantially reshape NPC structure and function, advancing our understanding of compositional and conformational NPC heterogeneity.

Selected Literature

1. Edvinas Stankunas & Alwin Köhler. Docking a flexible basket onto the core of the nuclear pore complex.  Nature Cell Biology Vol 26, Issue 9 (2024) https://doi.org/10.1038/s41556-024-01484-x
2. Petrovic S, Samanta D, Perriches T, Bley CJ, Thierbach K, Brown B, Nie S, Mobbs GW, Stevens TA, Liu X, Tomaleri GP, Schaus L, Hoelz A.  Architecture of the linker-scaffold in the nuclear pore. Science Vol 376, Issue 6598 (2022) https://doi.org/10.1126/science.abm9798
3. Mosalaganti S, Obarska-Kosinska A, Siggel M, Taniguchi R, Turoňová B, Zimmerli CE, Buczak K, Schmidt FH, Margiotta E, Mackmull MT, Hagen WJH, Hummer G, Kosinski J, Beck M. AI-based structure prediction empowers integrative structural analysis of human nuclear pores. Science Vol 376, Issue 6598 (2022) https://doi.org/10.1126/science.abm9506
4. Cibulka J, Bisaccia F, Radisavljević K, Gudino Carrillo RM, Köhler A. Assembly principle of a membrane-anchored nuclear pore basket scaffold. Science advances Vol 8, Issue 6, (2022) https://doi.org/10.1126/sciadv.abl6863
5. Bensidoun P, Zenklusen D, Oeffinger M. Choosing the right exit: How functional plasticity of the nuclear pore drives selective and efficient mRNA export. Wiley Interdiscip Rev RNA Vol 12, Issue 6 (2021) https://doi.org/10.1002/wrna.1660