8SP9

Crystal Structure of Coxsackievirus B3 (CVB3) Cloverleaf RNA with tRNA scaffold

Summary for 8SP9

• Entry DOI: 10.2210/pdb8sp9/pdb
• Descriptor: tRNA scaffold,CVB3 Cloverleaf RNA (1 entity in total)
• Functional Keywords: cloverleaf, base-triple, picornavirus, trna-scaffold, rna
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 1
• Total formula weight: 49187.06

Authors

Gottipati, K.,McNeme, S.C.,Choi, K.H. (deposition date: 2023-05-02, release date: 2023-08-09, Last modification date: 2023-09-20)

Primary citation

Gottipati, K.,McNeme, S.C.,Tipo, J.,White, M.A.,Choi, K.H.
Structural basis for cloverleaf RNA-initiated viral genome replication.
Nucleic Acids Res., 51:8850-8863, 2023

PubMed Abstract: The genomes of positive-strand RNA viruses serve as a template for both protein translation and genome replication. In enteroviruses, a cloverleaf RNA structure at the 5' end of the genome functions as a switch to transition from viral translation to replication by interacting with host poly(C)-binding protein 2 (PCBP2) and the viral 3CDpro protein. We determined the structures of cloverleaf RNA from coxsackievirus and poliovirus. Cloverleaf RNA folds into an H-type four-way junction and is stabilized by a unique adenosine-cytidine-uridine (A•C-U) base triple involving the conserved pyrimidine mismatch region. The two PCBP2 binding sites are spatially proximal and are located on the opposite end from the 3CDpro binding site on cloverleaf. We determined that the A•C-U base triple restricts the flexibility of the cloverleaf stem-loops resulting in partial occlusion of the PCBP2 binding site, and elimination of the A•C-U base triple increases the binding affinity of PCBP2 to the cloverleaf RNA. Based on the cloverleaf structures and biophysical assays, we propose a new mechanistic model by which enteroviruses use the cloverleaf structure as a molecular switch to transition from viral protein translation to genome replication.

PubMed: 37486760
DOI: 10.1093/nar/gkad618

Experimental method

X-RAY DIFFRACTION (2.92 Å)