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Crystal Structure of USP7 Ubiquitin-like Domains with an ICP0 Peptide Reveals a Novel Mechanism Used by Viral and Cellular Proteins to Target USP7


USP7 is a cellular protein that binds and stabilizes many proteins involved in multiple pathways that regulate oncogenesis and as such is recognized as a potential target for cancer therapy. In addition, USP7 is targeted by several viral proteins in order to promote cell survival and viral infection. One such protein is the ICP0 protein of herpes simplex virus 1, which must bind USP7 in order to manipulate the cell in ways that enable efficient viral infection. Here we use a structural approach to define the mechanism of the USP7-ICP0 peptide interaction, revealing a novel binding site on USP7. We then used this information to identify two cellular proteins, GMPS and UHRF1, that also bind USP7 through this binding site. Therefore we have identified a new mechanism by which both viral and cellular proteins can target USP7. This information will be useful for the development of strategies to block specific protein interactions with USP7.


Vyšlo v časopise: Crystal Structure of USP7 Ubiquitin-like Domains with an ICP0 Peptide Reveals a Novel Mechanism Used by Viral and Cellular Proteins to Target USP7. PLoS Pathog 11(6): e32767. doi:10.1371/journal.ppat.1004950
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004950

Souhrn

USP7 is a cellular protein that binds and stabilizes many proteins involved in multiple pathways that regulate oncogenesis and as such is recognized as a potential target for cancer therapy. In addition, USP7 is targeted by several viral proteins in order to promote cell survival and viral infection. One such protein is the ICP0 protein of herpes simplex virus 1, which must bind USP7 in order to manipulate the cell in ways that enable efficient viral infection. Here we use a structural approach to define the mechanism of the USP7-ICP0 peptide interaction, revealing a novel binding site on USP7. We then used this information to identify two cellular proteins, GMPS and UHRF1, that also bind USP7 through this binding site. Therefore we have identified a new mechanism by which both viral and cellular proteins can target USP7. This information will be useful for the development of strategies to block specific protein interactions with USP7.


Zdroje

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