9NLN

Crystal Structure of Coxsackievirus B3 IRES Domain V in Complex with a Fab

Summary for 9NLN

• Entry DOI: 10.2210/pdb9nln/pdb
• Descriptor: BL3-6 Fab Heavy Chain, BL3-6 Fab Light Chain, RNA (CVB3 IRES Domain V) (3 entities in total)
• Functional Keywords: ires rna, enterovirus, coxsackievirus b3, viral translation, viral rna, rna, rna-immune system complex, rna/immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 6
• Total formula weight: 169774.75

Authors

Das, N.K.,Banna, H.A.,Koirala, D. (deposition date: 2025-03-03, release date: 2026-02-18, Last modification date: 2026-05-06)

Primary citation

Banna, H.A.,Das, N.K.,Kalinina, M.,Lu, G.,Usman, M.,Koirala, D.
Structures of the eIF4G-binding RNA domains among picornaviral IRES types are topologically conserved.
Nat Commun, 17:-, 2026

PubMed Abstract: RNA domains within viral IRESs are crucial for initiating cap-independent translation of the genome in many positive-sense RNA viruses. However, the structures and mechanisms of these IRES domains remain unclear. Here, we present the 3 Å resolution crystal structure of the coxsackievirus B3 (CVB3) IRES domain V (dV) as a model for type I IRESs. The crystal structure revealed an elongated architecture of dV, with two sets of coaxially stacked stems forming an H-type four-way junction (4WJ) organized by an A-rich motif. Despite sequence dissimilarities, this dV from a type I IRES exhibits remarkable structural similarity to the analogous tertiary structures of the encephalomyocarditis virus (EMCV) JK domain and the hepatitis A virus (HAV) dV, which are typical domains in the type II and III IRESs, respectively. While SAXS studies indicate a similar RNA fold of dV in solution, structure-guided binding, computational modeling, and X-ray footprinting studies with and without the HEAT1 domain of eIF4G, compared to the analogous type II (EMCV JK) and III (HAV dV) domains, suggest that various IRESs maintain a common mechanism of eIF4G binding interactions during viral genome translation. Despite sequence variability, this structural conservation across IRES types may offer unique opportunities to develop universal antivirals targeting these structures.

PubMed: 41690908
DOI: 10.1038/s41467-026-69554-2

Experimental method

X-RAY DIFFRACTION (3 Å)