CM – Researchers are developing a model of the yeast nuclear pore complex


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January 3, 2022

from Boston University School of Medicine

Nuclear Pore Complexes (NPCs) are massive multiprotein complexes that act as passages for the transport of molecules into and out of the core. Given their central role in gene expression, growth, and development, it is not surprising that NPC defects have been linked to many diseases including viral infections, cancer, and certain neurodegenerative diseases, and that nuclear transport is a target for potential therapeutics.

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Researchers at Boston University School of Medicine (BUSM) have used rapid freezing and cryo-EM (electron microscopy) computational methods to create a comprehensive model of the yeast NPC showing the networked architecture of its core framework. This work provides molecular models for two configurations: one that is easier to study in isolated samples to give a more detailed overview of a radially compact form, and a second expanded form in the living yeast cell, although this is « in situ » details are currently being visualized at a lower level.

“This research significantly expands our understanding of the architecture of the brewer’s yeast NPC, a model organism used to study the biology of nucleated cells, and thus enables new insights into the Functions of this transport machine. « Explains corresponding author Christopher W. Akey, Ph.D., Professor of Physiology and Biophysics at BUSM.

According to researchers, this model will provide a better understanding of how these large mega-channels are composed and how they run through Bend extension of their central passage and adapt to changes in transport. “We also saw multiple types of NPC in the same cell for the first time, which reflects the Lego-like ability of this arrangement to use interchangeable parts to modify its architecture on the nuclear side. This adaptability could play a role in adapting « the capabilities of these machines to different local environments on the periphery of the core, » says Akey.

The researchers believe these results will now set the table for studies of how viruses do this important way of infecting cells and altering their physiology to cause disease.

These results appear online in the journal Cell.

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