9CSF

Structure of a dimeric ubiquitin variant (UbV3) that inhibits the protease (PRO) from Turnip Yellow Mosaic Virus (TYMV)

9CSF の概要

• エントリーDOI: 10.2210/pdb9csf/pdb
• 分子名称: Ubiquitin Variant UbV3, SULFATE ION (3 entities in total)
• 機能のキーワード: competitive inhibitor of tymv pro, ubiquitin variant, ubv3, viral protease, biosynthetic protein
• 由来する生物種: synthetic construct
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 23604.69

構造登録者

Kim, K.,Mark, B.L. (登録日: 2024-07-23, 公開日: 2025-01-22, 最終更新日: 2025-02-12)

主引用文献

De Silva, A.,Kim, K.,Weiland, J.,Hwang, J.,Chung, J.,Pereira, H.S.,Patel, T.R.,Teyra, J.,Patel, A.,Mira, M.M.,Khajehpour, M.,Bolton, M.,Stasolla, C.,Sidhu, S.S.,Mark, B.L.
Suppressing Tymovirus replication in plants using a variant of ubiquitin.
Plos Pathog., 21:e1012899-e1012899, 2025

PubMed Abstract: RNA viruses have evolved numerous strategies to overcome host resistance and immunity, including the use of multifunctional proteases that not only cleave viral polyproteins during virus replication but also deubiquitinate cellular proteins to suppress ubiquitin (Ub)-mediated antiviral mechanisms. Here, we report an approach to attenuate the infection of Arabidopsis thaliana by Turnip Yellow Mosaic Virus (TYMV) by suppressing the polyprotein cleavage and deubiquitination activities of the TYMV protease (PRO). Performing selections using a library of phage-displayed Ub variants (UbVs) for binding to recombinant PRO yielded several UbVs that bound the viral protease with nanomolar affinities and blocked its function. The strongest binding UbV (UbV3) candidate had a EC50 of 0.3 nM and inhibited both polyprotein cleavage and DUB activity of PRO in vitro. X-ray crystal structures of UbV3 alone and in complex with PRO reveal that the inhibitor exists as a dimer that binds two copies of PRO. Consistent with our biochemical and structural findings, transgenic expression of UbV3 in the cytosol of A. thaliana suppressed TYMV replication in planta, with the reduction in viral load being correlated to UbV3 expression level. Our results demonstrate the potential of using UbVs to protect plants from tymovirus infection, a family of viruses that contain numerous members of significant agricultural concern, as well as other plant viruses that express functionally related proteases with deubiquitinating activity.

PubMed: 39869641
DOI: 10.1371/journal.ppat.1012899

実験手法

X-RAY DIFFRACTION (1.84 Å)