Turnip yellow mosaic virus protease binds ubiquitin suboptimally to fine-tune its deubiquitinase activity
Turnip yellow mosaic virus protease binds ubiquitin suboptimally to fine-tune its deubiquitinase activity
Single-stranded, positive-sense RNA viruses assemble their replication complexes in infected cells from a multidomain replication polyprotein. This polyprotein usually contains at least one protease, the primary function of which is to process the polyprotein into mature proteins. Such proteases also may have other functions in the replication cycle. For instance, cysteine proteases (PRO) frequently double up as ubiquitin hydrolases (DUB), thus interfering with cellular processes critical for virus replication. We previously reported the crystal structures of such a PRO/DUB from Turnip yellow mosaic virus (TYMV) and of its complex with one of its PRO substrates. Here we report the crystal structure of TYMV PRO/DUB in complex with ubiquitin. We find that PRO/DUB recognizes ubiquitin in an unorthodox way: It interacts with the body of ubiquitin through a split recognition motif engaging both the major and the secondary recognition patches of ubiquitin (Ile44 patch and Ile36 patch, respectively, including Leu8, which is part of the two patches). However, the contacts are suboptimal on both sides. Introducing a single-point mutation in TYMV PRO/DUB aimed at improving ubiquitin-binding led to a much more active DUB. Comparison with other PRO/DUBs from other viral families, particularly coronaviruses, suggests that low DUB activities of viral PRO/DUBs may generally be fine-tuned features of interaction with host factors.
- French National Centre for Scientific Research France
- University of Paris-Saclay France
- Institut Jacques Monod France
- Université Paris-Saclay France
- UNIVERSITE PARIS DESCARTES France
crystal structure, Deubiquitinating Enzymes, Ubiquitin, protein complex, viral protease, Crystallography, X-Ray, [SDV] Life Sciences [q-bio], Viral Proteins, deubiquitylation (deubiquitination), plant virus, ubiquitin, Protein Structure and Folding, plus-stranded RNA virus, Tymovirus, Peptide Hydrolases
crystal structure, Deubiquitinating Enzymes, Ubiquitin, protein complex, viral protease, Crystallography, X-Ray, [SDV] Life Sciences [q-bio], Viral Proteins, deubiquitylation (deubiquitination), plant virus, ubiquitin, Protein Structure and Folding, plus-stranded RNA virus, Tymovirus, Peptide Hydrolases
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