Karyopherins remodel the dynamic organization of the nuclear pore complex transport barrier
Year: 2025
Type: article
Abstract: Nuclear pore complexes (NPCs) mediate selective exchange of macromolecules between the nucleus and cytoplasm, but the organization of their transport barrier has been a matter of debate. Here we used high-speed atomic force microscopy, complemented with orthogonal in vitro and in vivo approaches, to probe the dynamic behaviour of the NPC central channel at millisecond resolution. We found that nuclear transport factors dynamically remodel intrinsically disordered phenylalanine-glycine (FG) domains tethered within the NPC channel, partitioning the barrier into two zones: a rapidly fluctuating annular region and a highly mobile central plug. Increased FG-repeat density in mutant NPCs dampened barrier dynamics and impaired transport. Notably, NPC-like behaviour was recapitulated in DNA origami nanopores bearing transport factors and correctly tethered FG domains but not in in vitro FG hydrogels. Thus, the rotationally symmetric architecture of NPCs supports a nanoscopic barrier organization that contrasts with many of the bulk properties of in vitro FG-domain assemblies.
Source: Nature Cell Biology
Authors: Toshiya Kozai, Javier Fernandez-Martinez, Larisa E. Kapinos, Paola Gallardo, Trevor van Eeuwen, Martin Saladin, Roi Eliasian, Adam Mazur, Wenzhu Zhang, Jeremy Tempkin, Radhakrishnan Panatala, Maria Delgado-Izquierdo, Raul Escribano-Marin, Qingzhou Feng, Chenxiang Lin, Andrej Sali, Brian T. Chait, Barak Raveh, Liesbeth M. Veenhoff, Michael P. Rout, Roderick Y. H. Lim
Institutions: University of Basel, Swiss Nanoscience Institute, Ikerbasque, Consejo Superior de Investigaciones Científicas, University of the Basque Country, Instituto Biofisika, Fundación Biofísica Bizkaia, Rockefeller University, University Medical Center Groningen, University of Groningen, Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide, Hebrew University of Jerusalem, Lawrence Livermore National Laboratory, University of California, San Francisco, Yale University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $12,690
Funders: U.S. Department of Health and Human Services, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Nederlandse Organisatie voor Wetenschappelijk Onderzoek, Israel Science Foundation, National Institutes of Health, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases
Awards: IMP: Software for Hybrid Determination of Macromolecular Assembly Structures, G1181207698, National Center for Dynamic Interactome Research, G2147562158, G2717177379, G3741868197, G4129710062, Guardians of protein disorder, G517998402, Quality control of nuclear pores, Morphological dynamics of the permeability barrier in yeast nuclear pore complexes, Intermolecular forces in confined nanopores, G7433628105, A multiscale approach for elucidating nuclear entry mechanisms of HIV-1 capsid, The dynamic mechanism of nuclear transport visualized at the atomic scale, G81856226, G8690818240, G8793865596, Structure-Function Mapping of the Nuclear Pore Complex-Renewal
OpenAlex ID: W4416905520