Abstract

Nuclear pore complexes (NPCs) are highly selective filters that control the exchange of material between nucleus and cytoplasm. The principles that govern selective filtering by NPCs are not fully understood. Previous studies find that cellular proteins capable of fast translocation through NPCs (transport receptors) are characterized by a high proportion of hydrophobic surface regions. Our analysis finds that transport receptors and their complexes are also highly negatively charged. Moreover, NPC components that constitute the permeability barrier are positively charged. We estimate that electrostatic interactions between a transport receptor and the NPC result in an energy gain of several k B T, which would enable significantly increased translocation rates of transport receptors relative to other cellular proteins. We suggest that negative charge is an essential criterion for selective passage through the NPC.

Highlights

  • The defining feature of eukaryotic cells is the separation of nuclear and cytoplasmic compartments by the nuclear envelope

  • The transport of material between the nucleus and cytoplasm occurs through nuclear pore complexes (NPCs), aqueous channels that are embedded in the nuclear envelope

  • All proteins that move between the cytoplasm and the nucleus must pass through nuclear pore complexes, large aqueous channels around 40nm in diameter

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Summary

Introduction

The defining feature of eukaryotic cells is the separation of nuclear and cytoplasmic compartments by the nuclear envelope. For example polymerases and transcription factors, are made in the cytoplasm and imported into the nucleus. RNAs that function in translation are made inside the nucleus and exported to the cytoplasm. The transport of material between the nucleus and cytoplasm occurs through nuclear pore complexes (NPCs), aqueous channels that are embedded in the nuclear envelope. Translocation through NPCs is fully reversible and uncoupled from NTP hydrolysis [1,2,3,4,5]. Kinetic measurements demonstrate that a single NPC can selectively translocate nearly one thousand molecules per second [6,7]

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