9D9P
Crystal structure of CVB3 replication-linked RNA in complex with 3C protein
Summary for 9D9P
| Entry DOI | 10.2210/pdb9d9p/pdb |
| Descriptor | RNA (90-MER), Protease 3C, PHOSPHATE ION, ... (4 entities in total) |
| Functional Keywords | cloverleaf rna-3c protein complex, viral replication, enterovirus, coxsackievirus, viral rna, 3c proteinase, rna, viral protein-rna complex, viral protein/rna |
| Biological source | Coxsackievirus B3 More |
| Total number of polymer chains | 3 |
| Total formula weight | 72201.01 |
| Authors | Das, N.K.,Koirala, D. (deposition date: 2024-08-21, release date: 2025-10-01, Last modification date: 2026-04-01) |
| Primary citation | Das, N.K.,Patel, A.,Abdelghani, R.,Koirala, D. Structural basis for 3C and 3CD recruitment by enteroviral genomes during negative-strand RNA synthesis. Nat Commun, 16:9293-9293, 2025 Cited by PubMed Abstract: Enteroviral replication-linked cloverleaf RNAs recruit the viral 3CD protein, a fusion of 3C protease and 3D RNA-dependent RNA-polymerase, for negative-strand synthesis during genome replication. However, the structures and mechanisms of this virological process remain unclear. Using the coxsackievirus B3 model, we determine the crystal structures of both intact cloverleaf-3C and isolated sD-3C complexes at 2.69 Å and 2.41 Å resolutions, respectively. Our structures reveal that the sD stem-loop is the sole determinant for binding two 3C monomers, with each monomer recognizing the lateral surface of the sD stem either upstream (toward the apical tetraloop) or downstream (near the dinucleotide bulge) of the Py•Py helix. Binding studies with structure-guided cloverleaf and 3C mutants further clarify the roles of specific nucleotides and residues involved in the interactions between cloverleaf and 3C, explaining earlier virological observations. Through comparative structural and binding studies of 3C, 3D, and 3CD with cloverleafs from seven different enteroviral species, we demonstrate that while the 3D domain does not contribute to cloverleaf binding, the sD sequence and its structural pattern govern 3CD-cloverleaf interactions through the 3C domain. Our work establishes a high-resolution structural framework for understanding enteroviral replication mechanisms, which will aid in developing antivirals targeting this platform. PubMed: 41120315DOI: 10.1038/s41467-025-64376-0 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.69 Å) |
Structure validation
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