Docking a Flexible Basket Onto the Core of the Nuclear Pore Complex

Overview

Journal Nat Cell Biol

Specialty Cell Biology

Date 2024 Aug 13

PMID 39138317

Authors

Edvinas Stankunas

Alwin Kohler

Affiliations

Soon will be listed here.

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-complex•Nup60•Mlp1 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.

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References

GOLDBERG M, ALLEN T . The nuclear pore complex and lamina: three-dimensional structures and interactions determined by field emission in-lens scanning electron microscopy. J Mol Biol. 1996; 257(4):848-65. DOI: 10.1006/jmbi.1996.0206. View

RIS H . High-resolution field-emission scanning electron microscopy of nuclear pore complex. Scanning. 1997; 19(5):368-75. DOI: 10.1002/sca.4950190504. View

Beck M, Forster F, Ecke M, Plitzko J, Melchior F, Gerisch G . Nuclear pore complex structure and dynamics revealed by cryoelectron tomography. Science. 2004; 306(5700):1387-90. DOI: 10.1126/science.1104808. View

Krull S, Dorries J, Boysen B, Reidenbach S, Magnius L, Norder H . Protein Tpr is required for establishing nuclear pore-associated zones of heterochromatin exclusion. EMBO J. 2010; 29(10):1659-73. PMC: 2876962. DOI: 10.1038/emboj.2010.54. View

Niepel M, Molloy K, Williams R, Farr J, Meinema A, Vecchietti N . The nuclear basket proteins Mlp1p and Mlp2p are part of a dynamic interactome including Esc1p and the proteasome. Mol Biol Cell. 2013; 24(24):3920-38. PMC: 3861087. DOI: 10.1091/mbc.E13-07-0412. View

Saroufim M, Bensidoun P, Raymond P, Rahman S, Krause M, Oeffinger M . The nuclear basket mediates perinuclear mRNA scanning in budding yeast. J Cell Biol. 2015; 211(6):1131-40. PMC: 4687876. DOI: 10.1083/jcb.201503070. View

Green D, Johnson C, Hagan H, Corbett A . The C-terminal domain of myosin-like protein 1 (Mlp1p) is a docking site for heterogeneous nuclear ribonucleoproteins that are required for mRNA export. Proc Natl Acad Sci U S A. 2003; 100(3):1010-5. PMC: 298717. DOI: 10.1073/pnas.0336594100. View

Galy V, Gadal O, Fromont-Racine M, Romano A, Jacquier A, Nehrbass U . Nuclear retention of unspliced mRNAs in yeast is mediated by perinuclear Mlp1. Cell. 2004; 116(1):63-73. DOI: 10.1016/s0092-8674(03)01026-2. View

Albert S, Schaffer M, Beck F, Mosalaganti S, Asano S, Thomas H . Proteasomes tether to two distinct sites at the nuclear pore complex. Proc Natl Acad Sci U S A. 2017; 114(52):13726-13731. PMC: 5748218. DOI: 10.1073/pnas.1716305114. View

10.

Schneider M, Hellerschmied D, Schubert T, Amlacher S, Vinayachandran V, Reja R . The Nuclear Pore-Associated TREX-2 Complex Employs Mediator to Regulate Gene Expression. Cell. 2015; 162(5):1016-28. PMC: 4644235. DOI: 10.1016/j.cell.2015.07.059. View

11.

Aksenova V, Smith A, Lee H, Bhat P, Esnault C, Chen S . Nucleoporin TPR is an integral component of the TREX-2 mRNA export pathway. Nat Commun. 2020; 11(1):4577. PMC: 7486939. DOI: 10.1038/s41467-020-18266-2. View

12.

Denning D, Patel S, Uversky V, Fink A, Rexach M . Disorder in the nuclear pore complex: the FG repeat regions of nucleoporins are natively unfolded. Proc Natl Acad Sci U S A. 2003; 100(5):2450-5. PMC: 151361. DOI: 10.1073/pnas.0437902100. View

13.

Pyhtila B, Rexach M . A gradient of affinity for the karyopherin Kap95p along the yeast nuclear pore complex. J Biol Chem. 2003; 278(43):42699-709. DOI: 10.1074/jbc.M307135200. View

14.

Strawn L, Shen T, Shulga N, Goldfarb D, Wente S . Minimal nuclear pore complexes define FG repeat domains essential for transport. Nat Cell Biol. 2004; 6(3):197-206. DOI: 10.1038/ncb1097. View

15.

Meszaros N, Cibulka J, Mendiburo M, Romanauska A, Schneider M, Kohler A . Nuclear pore basket proteins are tethered to the nuclear envelope and can regulate membrane curvature. Dev Cell. 2015; 33(3):285-98. PMC: 4425464. DOI: 10.1016/j.devcel.2015.02.017. View

16.

Bensidoun P, Reiter T, Montpetit B, Zenklusen D, Oeffinger M . Nuclear mRNA metabolism drives selective basket assembly on a subset of nuclear pore complexes in budding yeast. Mol Cell. 2022; 82(20):3856-3871.e6. PMC: 10300651. DOI: 10.1016/j.molcel.2022.09.019. View

17.

DAngelo M, Sebastian Gomez-Cavazos J, Mei A, Lackner D, Hetzer M . A change in nuclear pore complex composition regulates cell differentiation. Dev Cell. 2012; 22(2):446-58. PMC: 3288503. DOI: 10.1016/j.devcel.2011.11.021. View

18.

Akey C, Echeverria I, Ouch C, Nudelman I, Shi Y, Wang J . Implications of a multiscale structure of the yeast nuclear pore complex. Mol Cell. 2023; 83(18):3283-3302.e5. PMC: 10630966. DOI: 10.1016/j.molcel.2023.08.025. View

19.

Akey C, Singh D, Ouch C, Echeverria I, Nudelman I, Varberg J . Comprehensive structure and functional adaptations of the yeast nuclear pore complex. Cell. 2022; 185(2):361-378.e25. PMC: 8928745. DOI: 10.1016/j.cell.2021.12.015. View

20.

Daigle N, Beaudouin J, Hartnell L, Imreh G, Hallberg E, Lippincott-Schwartz J . Nuclear pore complexes form immobile networks and have a very low turnover in live mammalian cells. J Cell Biol. 2001; 154(1):71-84. PMC: 2196857. DOI: 10.1083/jcb.200101089. View