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

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.

SUBMITTER: da Fonseca PC

PROVIDER: S-EPMC4506541 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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

da Fonseca Paula C A PC Morris Edward P EP

Nature communications 20150702

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 coord ...[more]

PMID: 26133119

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