8KI7

Structure of Tomato spotted wilt virus L protein contained endoH domain binding to 3'5'vRNA

Summary for 8KI7

• Entry DOI: 10.2210/pdb8ki7/pdb
• EMDB information: 37253
• Descriptor: RNA-directed RNA polymerase L, RNA (5'-R(P*AP*GP*AP*GP*CP*AP*AP*UP*CP*A)-3'), RNA (5'-R(P*GP*CP*AP*AP*UP*CP*AP*GP*G)-3'), ... (4 entities in total)
• Functional Keywords: tomato spotted wilt virus, l protein, viral protein, viral protein-rna complex, viral protein/rna
• Biological source: Tomato spotted wilt virus (strain Bulgarian L3) (TSWV); More
• Total number of polymer chains: 4
• Total formula weight: 250536.61

Authors

Cao, L.,Wang, X. (deposition date: 2023-08-23, release date: 2024-09-25, Last modification date: 2025-04-09)

Primary citation

Li, J.,Cao, L.,Zhao, Y.,Shen, J.,Wang, L.,Feng, M.,Zhu, M.,Ye, Y.,Kormelink, R.,Tao, X.,Wang, X.
Structural basis for the activation of plant bunyavirus replication machinery and its dual-targeted inhibition by ribavirin.
Nat.Plants, 11:518-530, 2025

PubMed Abstract: Despite the discovery of plant viruses as a new class of pathogens over a century ago, the structure of plant virus replication machinery and antiviral pesticide remains lacking. Here we report five cryogenic electron microscopy structures of a ~330-kDa RNA-dependent RNA polymerase (RdRp) from a devastating plant bunyavirus, tomato spotted wilt orthotospovirus (TSWV), including the apo, viral-RNA-bound, base analogue ribavirin-bound and ribavirin-triphosphate-bound states. They reveal that a flexible loop of RdRp's motif F functions as 'sensor' to perceive viral RNA and further acts as an 'adaptor' to promote the formation of a complete catalytic centre. A ten-base RNA 'hook' structure is sufficient to trigger major conformational changes and activate RdRp. Chemical screening showed that ribavirin is effective against TSWV, and structural data revealed that ribavirin disrupts both hook-binding and catalytic core formation, locking polymerase in its inactive state. This work provides structural insights into the mechanisms of plant bunyavirus RdRp activation and its dual-targeted site inhibition, facilitating the development of pesticides against plant viruses.

PubMed: 40044941
DOI: 10.1038/s41477-025-01940-y

Experimental method

ELECTRON MICROSCOPY (3.7 Å)