Cryo-EM reveals the conformation of a substrate analogue in the human 20S proteasome core

da Fonseca, P. C.A. and Morris, E. P. (2015) Cryo-EM reveals the conformation of a substrate analogue in the human 20S proteasome core. Nature Communications, 6, 7573. (doi: 10.1038/ncomms8573) (PMID:26133119) (PMCID:PMC4506541)

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Abstract

The proteasome is a highly regulated protease complex fundamental for cell homeostasis and controlled cell cycle progression. It functions by removing a wide range of specifically tagged proteins, including key cellular regulators. Here we present the structure of the human 20S proteasome core bound to a substrate analogue inhibitor molecule, determined by electron cryo-microscopy (cryo-EM) and single-particle analysis at a resolution of around 3.5 Å. Our map allows the building of protein coordinates as well as defining the location and conformation of the inhibitor at the different active sites. These results open new prospects to tackle the proteasome functional mechanisms. Moreover, they also further demonstrate that cryo-EM is emerging as a realistic approach for general structural studies of protein–ligand interactions.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:da Fonseca, Professor Paula
Authors: da Fonseca, P. C.A., and Morris, E. P.
College/School:College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
Journal Name:Nature Communications
Publisher:Nature Publishing Group
ISSN:2041-1723
ISSN (Online):2041-1723
Copyright Holders:Copyright © 2015 Macmillan Publishers Limited
First Published:First published in Nature Communications 6(1):7573
Publisher Policy:Reproduced under a Creative Commons licence

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