9UZK

EMCV IRES captured on mammalian 40S with initiator tRNA

Summary for 9UZK

• Entry DOI: 10.2210/pdb9uzk/pdb
• EMDB information: 64644
• Descriptor: 18S ribosomal RNA, Small ribosomal subunit protein eS8, Small ribosomal subunit protein uS4, ... (37 entities in total)
• Functional Keywords: emcv ires, 40s ribosome, 48s pic, ribosome
• Biological source: Encephalomyocarditis virus; More
• Total number of polymer chains: 37
• Total formula weight: 1276944.84

Authors

Das, D.,Hussain, T. (deposition date: 2025-05-16, release date: 2026-05-27, Last modification date: 2026-07-08)

Primary citation

Das, D.,Hussain, T.
Structural insights into the recruitment of viral type 2 IRES to ribosomal preinitiation complex for protein synthesis.
Elife, 14:-, 2026

PubMed Abstract: Picornaviruses employ internal ribosome entry sites (IRESs) in their genomic RNA to hijack the host's translational machinery. The picornavirus, encephalomyocarditis virus, employs a type 2 IRES present in its 5' untranslated region (5'UTR) and requires 43S ribosomal preinitiation complex (PIC), the central domain of eukaryotic initiation factor (eIF) 4G, eIF4A, and an essential ITAF (IRES trans-acting factor)-polypyrimidine tract binding protein 1 (PTB1) to form 48S PIC. In this study, we have used cryo-electron microscopy (cryo-EM) to determine the structure of encephalomyocarditis virus (EMCV) IRES-bound mammalian 48S PIC in a scanning-arrested closed state at the start codon. The EMCV IRES domains contact initiator tRNA (tRNA) and 40S head at the inter-subunit interface, which reveals an altogether unique mechanism used by viruses to capture host translational machinery for its protein synthesis. The tRNA is held away from the 40S body in contrast to canonical cap-dependent translation while the domain I apical region of EMCV IRES mimics 28S rRNA of 60S to interact with 40S ribosomal head proteins uS13 and uS19. The structural analysis accounts for numerous previously reported biochemical studies on type 2 IRES and shows how type 2 IRES interacts with 43S PIC to form 48S PIC. This study provides mechanistic insights for understanding EMCV IRES-mediated translation initiation, which could be extrapolated to other IRESs sharing similar motifs and factor requirements, including type 1 viral IRESs.

PubMed: 42345371
DOI: 10.7554/eLife.107788

Experimental method

ELECTRON MICROSCOPY (4.6 Å)