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Viral deubiquitylation: toning things down brings better control?

A study led by a team from the Institut Joliot (I2BC/B3S) reveals an unusual mode of interaction between a viral deubiquitinase and a ubiquitin, which appears to be optimized to finely control virus replication. 

Published on 8 September 2020

​In order to fight a viral attack, infected cells often add poly-ubiquitin chains to some viral proteins in order to send them to the proteasome where they will be degraded. Some viruses have developed deubiquitinases (DUBs), either to counteract antiviral mechanisms or to promote their replication. The targets of viral DUBs may be cellular proteins. In this case, the aim is for the virus to reduce the production of various antiviral molecules such as interferons or cytokines and to escape the host's immune responses. Targets can also be viral proteins, partly to simply "save" them from degradation and partly because, in some cases, fine control of their level of expression is necessary for the virus to maintain effective replication. This is the case of Turnip yellow mosaic virus (TYMV) whose RNA-dependent RNA polymerase (RdRp) is successively poly-ubiquitinylated by infected plant cells and then deubiquitinylated by the DUB encoded by the virus itself.

In an article published in the Journal of Biological Chemistry, researchers from I2BC (Department B3S, Université Paris-Saclay, CEA, CNRS), in collaboration with the Institut Jacques Monod and Harvard Medical School, have resolved the crystal structure of a complex formed between the TYMV DUB and a ubiquitin molecule (resolution at 3.7 Å). Complemented by molecular dynamics simulations, this structure shows unusual features, including polar surfaces of the TYMV DUB in contact with hydrophobic surfaces of the ubiquitin. Point mutants have a surprisingly increased DUB activity, showing that the interaction surfaces involved in the DUB-ubiquitin complex are suboptimal.

The overall results indicate that the low DUB activity of TYMV would be an evolutionary compromise allowing a perfect adjustment of the level of expression of RdRp and thus the amount of replicated viral genome. This phenomenon seems to be extrapolated to other viruses, notably coronaviruses, which also use deubiquitinylation to control the expression of proteins necessary for the replication of their genome.

Contact: Sonia Fieulaine

This text is a translation and an adaptation of the news published on  « Life Sciences Université Paris-Saclay » feed:

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