Exploring Cellular Gateways: Unraveling the Secrets of Disordered Proteins Within Live Nuclear Pores

Overview

Journal Res Sq

Date 2024 Jan 23

PMID 38260360

Authors

Wenlan Yu

Mark Tingey

Joseph M Kelich

Yichen Li

Jingjie Yu

Samuel L Junod

Zecheng Jiang

Ian Hansen

Nacef Good

Weidong Yang

Affiliations

Soon will be listed here.

Abstract

Understanding the spatial organization of nucleoporins (Nups) with intrinsically disordered domains within the nuclear pore complex (NPC) is crucial for deciphering eukaryotic nucleocytoplasmic transport. Leveraging high-speed 2D single-molecule tracking and virtual 3D super-resolution microscopy in live HeLa cells, we investigated the spatial distribution of all eleven phenylalanine-glycine (FG)-rich Nups within individual NPCs. Our study reveals a nuanced landscape of FG-Nup conformations and arrangements. Five FG-Nups are steadfastly anchored at the NPC scaffold, collectively shaping a central doughnut-shaped channel, while six others exhibit heightened flexibility, extending towards the cytoplasmic and nucleoplasmic regions. Intriguingly, Nup214 and Nup153 contribute to cap-like structures that dynamically alternate between open and closed states along the nucleocytoplasmic transport axis, impacting the cytoplasmic and nuclear sides, respectively. Furthermore, Nup98, concentrated at the scaffold region, extends throughout the entire NPC while overlapping with other FG-Nups. Together, these eleven FG-Nups compose a versatile, capped trichoid channel spanning approximately 270 nm across the nuclear envelope. This adaptable trichoid channel facilitates a spectrum of pathways for passive diffusion and facilitated nucleocytoplasmic transport. Our comprehensive mapping of FG-Nup organization within live NPCs offers a unifying mechanism accommodating multiple transport pathways, thereby advancing our understanding of cellular transport processes.

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